Molecules

12 pages, 1761 KiB

Open AccessArticle

Bioactivity of a Novel Glycolipid Produced by a Halophilic Buttiauxella sp. and Improving Submerged Fermentation Using a Response Surface Method

by Abdolrazagh Marzban¹, Gholamhossein Ebrahimipour² and Abolghasem Danesh^1,*

¹ Biotechnology Research Center, Mashhad University of Medical Sciences, Mashhad 91775-1365, Iran

² Department of Microbiology, Faculty of Biological Sciences, Shahid Beheshti University, Tehran 19839-4716, Iran

Molecules 2016, 21(10), 1256; https://doi.org/10.3390/molecules21101256 - 22 Sep 2016

Cited by 32 | Viewed by 6479

Abstract

An antimicrobial glycolipid biosurfactant (GBS), extracted and identified from a marine bacterium, was studied to inhibit pathogenic microorganisms. Production of the GBS was optimized using a statistical method, a response surface method (RSM) with a central composite design (CCD) for obtaining maximum yields [...] Read more.

An antimicrobial glycolipid biosurfactant (GBS), extracted and identified from a marine bacterium, was studied to inhibit pathogenic microorganisms. Production of the GBS was optimized using a statistical method, a response surface method (RSM) with a central composite design (CCD) for obtaining maximum yields on a cost-effective substrate, molasses. The GBS-producing bacterium was identified as Buttiauxella Species in terms of biochemical and molecular characteristics. This compound showed a desirable antimicrobial activity against some pathogens such as E. coli, Bacillus subtilis, Bacillus cereus, Candida albicans, Aspergilus niger, Salmonella enterica. The rheological studies described the stability of the GBS at high values in a range of pH (7–8), temperature (20–60) and salinity (0%–3%). The statistical optimization of GBS fermentation was found to be pH 7, temperature 33 °C, Peptone 1%, NaCl 1% and molasses 1%. The potency of the GBS as an effective antimicrobial agent provides evidence for its use against food and human pathogens. Moreover, favorable production of the GBS in the presence of molasses as a cheap substrate and the feasibility of pilot scale fermentation using an RSM method could expand its uses in food, pharmaceutical products and oil industries. Full article

(This article belongs to the Section Metabolites)

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12 pages, 10511 KiB

Open AccessArticle

Effects of Sanguis Draconis on Perforator Flap Survival in Rats

by Yang Zhang^1,†, Xiaobing Cai^2,†, Lifeng Shen³, Xiaowen Huang¹, Xuping Wang¹, Yinan Lan² and Dan Shou^1,*

¹ Department of Medicine, Zhejiang Academy of Traditional Chinese Medicine, Hangzhou 310007, Zhejiang, China

² Department of Orthopedic Surgery, Lishui Central Hospital, Lishui 323000, Zhejiang, China

³ Department of Orthopedic Surgery, Zhejiang Provincial Tongde Hospital, Hangzhou 310012, Zhejiang, China

Molecules 2016, 21(10), 1262; https://doi.org/10.3390/molecules21101262 - 26 Sep 2016

Cited by 6 | Viewed by 6079

Abstract

Sanguis draconis, a resin known to improve blood circulation, relieve pain, stimulate tissue regeneration, and heal wounds, is widely used in clinical practice. In this study, we prepared an ethanol extract of sanguis draconis (EESD) containing 75.08 mg/g of dracorhodin. The experiment was [...] Read more.

Sanguis draconis, a resin known to improve blood circulation, relieve pain, stimulate tissue regeneration, and heal wounds, is widely used in clinical practice. In this study, we prepared an ethanol extract of sanguis draconis (EESD) containing 75.08 mg/g of dracorhodin. The experiment was carried out on 20 rats that were divided into two groups, a control group (n = 10) and an EESD group (n = 10). All the rats underwent a perforator flap surgery, after which post-operative abdominal compressions of EESD were given to the EESD group for seven days, while the control group received saline. Flap survival percentages were determined after seven days, and were found to be significantly higher in the EESD group than in the control group. Results of laser Doppler flowmetry (LDF) showed that perforator flaps in the EESD group had higher perfusion values than those of the control group. The flap tissues were stained with hematoxylin and eosin, followed by immunohistochemical evaluation. Superoxide dismutase (SOD) expression and micro-vessel development markedly increased in the EESD group, while malondialdehyde (MDA) levels decreased. This is the first study to investigate the effect of sanguis draconis on perforator flap survival. Our results demonstrate that sanguis draconis can improve perforator flap survival in rats by promoting microvessel regeneration and blood perfusion. Full article

(This article belongs to the Collection Herbal Medicine Research)

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14 pages, 1202 KiB

Open AccessCommunication

Identification of Metabolites of 6′-Hydroxy-3,4,5,2′,4′-pentamethoxychalcone in Rats by a Combination of Ultra-High-Performance Liquid Chromatography with Linear Ion Trap-Orbitrap Mass Spectrometry Based on Multiple Data Processing Techniques

by Siyi Liu^1,†, Yanyun Che^2,†, Fei Wang¹, Zhanpeng Shang¹, Jianqiu Lu¹, Shengyun Dai¹, Jiayu Zhang^1,* and Wei Cai^3,*

¹ School of Chinese Pharmacy, Beijing University of Chinese Medicine, 11 East Road of North 3rd Ring, Chaoyang District, Beijing 100029, China

² School of Chinese Pharmacy, Yunnan University of Traditional Chinese Medicine, Kunming 650500, China

³ Department of Pharmacy, Hunan University of Medicine, Huaihua 41800, China

Molecules 2016, 21(10), 1266; https://doi.org/10.3390/molecules21101266 - 22 Sep 2016

Cited by 16 | Viewed by 5243

Abstract

In this study, an efficient strategy was established using ultra-high-performance liquid chromatography coupled with linear ion trap-Orbitrap mass spectrometry (UHPLC-LTQ-Orbitrap MS) to profile the in vivo metabolic fate of 6′-hydroxy-3,4,5,2′,4′-pentamethoxychalcone (PTC) in rat urine and feces. The UHPLC-LTQ-Orbitrap method combines the high trapping [...] Read more.

In this study, an efficient strategy was established using ultra-high-performance liquid chromatography coupled with linear ion trap-Orbitrap mass spectrometry (UHPLC-LTQ-Orbitrap MS) to profile the in vivo metabolic fate of 6′-hydroxy-3,4,5,2′,4′-pentamethoxychalcone (PTC) in rat urine and feces. The UHPLC-LTQ-Orbitrap method combines the high trapping capacity and MSⁿ scanning function of the linear ion trap along with accurate mass measurements within 5 ppm and a resolving power of up to 30,000 over a wider dynamic range compared to many other mass spectrometers. In order to reduce the potential interferences of endogenous substances, the post-acquisition processing method including high-resolution extracted ion chromatogram (HREIC) and multiple mass defect filters (MMDF) were developed for metabolite detection. As a result, a total of 60 and 35 metabolites were detected in the urine and feces, respectively. The corresponding in vivo reactions such as methylation, hydroxylation, hydrogenation, decarbonylation, demethylation, dehydration, methylation, demethoxylation, sulfate conjugation, glucuronide conjugation, and their composite reactions were all detected in this study. The result on PTC metabolites significantly expanded the understanding of its pharmacological effects, and could be targets for future studies on the important chemical constituents from herbal medicines. Full article

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9 pages, 2014 KiB

Open AccessArticle

Cordycepin Induces Apoptosis and Inhibits Proliferation of Human Lung Cancer Cell Line H1975 via Inhibiting the Phosphorylation of EGFR

by Zheng Wang^1,*,†, Xue Wu^2,†, Yan-Ni Liang^1,†, Li Wang¹, Zhong-Xing Song¹, Jian-Li Liu³ and Zhi-Shu Tang^1,*

¹ Shaanxi Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Shaanxi Province Key Laboratory of New Drugs and Chinese Medicine Foundation Research, Shaanxi Rheumatism and Tumor Center of TCM Engineering Technology Research, Shaanxi University of Chinese Medicine, Xian Yang 712083, China

² Department of Burns and Cutaneous Surgery, Xijing Hospital, Xi’an 710032, China

³ Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, College of Life Science, Northwest University, Xi’an 710069, China

Molecules 2016, 21(10), 1267; https://doi.org/10.3390/molecules21101267 - 27 Sep 2016

Cited by 56 | Viewed by 8355

Abstract

Cordycepin is an active component of the traditional Chinese medicine Cordyceps sinensis and Cordyceps militaris with notable anticancer activity. Though the prominent inhibitory activity was reported in different kinds of cancer cell lines, the concrete mechanisms remain elusive. It was reported that cordycepin [...] Read more.

Cordycepin is an active component of the traditional Chinese medicine Cordyceps sinensis and Cordyceps militaris with notable anticancer activity. Though the prominent inhibitory activity was reported in different kinds of cancer cell lines, the concrete mechanisms remain elusive. It was reported that cordycepin could be converted into tri-phosphates in vivo to confuse a number of enzymes and interfere the normal cell function. For the inhibitory mechanism of EGFR inhibitors and the structure similarity of ATP and tri-phosphated cordycepin, human lung cancer cell line H1975 was employed to investigate the inhibitory effect of cordycepin. The results showed that cordycepin could inhibit cell proliferation and induce apoptosis in a dose-dependent manner. Cell cycle analysis revealed that H1975 cells could be arrested at the G₀/G₁ phase after cordycepin treatment. The expression levels of apoptosis-related protein Caspase-3 and Bcl-2 and phosphorylated expression levels of EGFR, AKT and ERK1/2 were all decreased compared with the control group stimulated with EGF. However, the protein expression levels of proapoptotic protein Bax and cleaved caspase-3 were increased. These results implied that cordycepin could inhibit cell proliferation and induce apoptosis via the EGFR signaling pathway. Our results indicated that there was potential to seek a novel EGFR inhibitor from cordycepin and its chemical derivatives. Full article

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7 pages, 457 KiB

Open AccessCommunication

Palladium-Catalyzed C–H Arylation of 1,2,3-Triazoles

by Chengwei Zhang, Lin You and Chuo Chen^*

Department of Biochemistry, UT Southwestern Medical Center, Dallas, TX 75390, USA

Molecules 2016, 21(10), 1268; https://doi.org/10.3390/molecules21101268 - 22 Sep 2016

Cited by 7 | Viewed by 5340

Abstract

Palladium(II) acetate, in combination with triphenylphosphine, catalyzes direct arylation of 1,4-disubstituted 1,2,3-triazoles effectively. This C–H arylation reaction provides facile access to fully substituted triazoles with well-defined regiochemistry. Full article

(This article belongs to the Special Issue Reactions of Hydrocarbons and other C‒H Compounds)

21 pages, 2790 KiB

Open AccessArticle

Efficacy of Pre- and Post-Treatment by Topical Formulations Containing Dissolved and Suspended Silybum marianum against UVB-Induced Oxidative Stress in Guinea Pig and on HaCaT Keratinocytes

by Pálma Fehér¹, Zoltán Ujhelyi¹, Judit Váradi¹, Ferenc Fenyvesi¹, Eszter Róka¹, Béla Juhász², Balázs Varga², Mariann Bombicz², Dániel Priksz², Ildikó Bácskay^1,* and Miklós Vecsernyés¹

¹ Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Debrecen, Nagyerdei körút 98, 4032 Debrecen, Hungary

² Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, University of Debrecen, Nagyerdei körút 98, 4032 Debrecen, Hungary

Molecules 2016, 21(10), 1269; https://doi.org/10.3390/molecules21101269 - 22 Sep 2016

Cited by 36 | Viewed by 7338

Abstract

Plants with high amounts of antioxidants may be a promising therapy for preventing and curing UV-induced oxidative skin damage. The objective of this study was to verify the efficacy of topical formulations containing dissolved and suspended Silybum marianum extract against UVB-induced oxidative stress [...] Read more.

Plants with high amounts of antioxidants may be a promising therapy for preventing and curing UV-induced oxidative skin damage. The objective of this study was to verify the efficacy of topical formulations containing dissolved and suspended Silybum marianum extract against UVB-induced oxidative stress in guinea pig and HaCaT keratinocytes. Herbal extract was dissolved in Transcutol HP (TC) and sucrose-esters were incorporated as penetration enhancers in creams. Biocompatibility of compositions was tested on HeLa cells and HaCaT keratinocytes as in vitro models. Transepidermal water loss (TEWL) tests were performed to prove the safety of formulations in vivo. Drug release of different compositions was assessed by Franz diffusion methods. Superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and lipid peroxidation (MDA) activities were evaluated before and after UVB irradiation in a guinea pig model and HaCaT cells. Heme oxygenase-1 (HO-1) enzyme activity was measured in the epidermis of guinea pigs treated by different creams before and after UVB irradiation. Treatment with compositions containing silymarin powder (SM) dissolved in TC and sucrose stearate SP 50 or SP 70 resulted in increased activities of all reactive oxygen species (ROS) eliminating enzymes in the case of pre- and post-treatment as well. Reduction in the levels of lipid peroxidation end products was also detected after treatment with these two compositions. Post-treatment was more effective as the increase of the activity of antioxidants was higher. Lower HO-1 enzyme levels were measured in the case of pre- and post-treatment groups compared to control groups. Therefore, this study demonstrates the effectiveness of topical formulations containing silymarin in inhibiting UVB irradiation induced oxidative stress of the skin. Full article

(This article belongs to the Special Issue Silymarin)

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11 pages, 2387 KiB

Open AccessArticle

Structural Characterization of the Avidin Interactions with Fluorescent Pyrene-Conjugates: 1-Biotinylpyrene and 1-Desthiobiotinylpyrene

by Paweł Strzelczyk¹, Damian Plażuk²

, Janusz Zakrzewski² and Grzegorz Bujacz^1,*

¹ Institute of Technical Biochemistry, Faculty of Biotechnology and Food Sciences, Lodz University of Technology, 90-924 Łódź, Stefanowskiego 4/10, Poland

² Department of Organic Chemistry, Faculty of Chemistry, University of Lodz, 91-403 Łódź, Tamka 12, Poland

Molecules 2016, 21(10), 1270; https://doi.org/10.3390/molecules21101270 - 27 Sep 2016

Cited by 8 | Viewed by 6435

Abstract

Avidin is a tetrameric protein that belongs to the calycin superfamily. It has been studied mainly because of its extraordinary affinity to biotin, which led to a wide range of applications based on the avidin-biotin system. In the present study, we report the [...] Read more.

Avidin is a tetrameric protein that belongs to the calycin superfamily. It has been studied mainly because of its extraordinary affinity to biotin, which led to a wide range of applications based on the avidin-biotin system. In the present study, we report the first crystal structures of avidin in a complex with two novel fluorescent pyrene derivatives: 1-biotinylpyrene (B9P) and 1-desthiobiotinylpyrene (D9P). The crystal structures were solved by molecular replacement using the coordinates of avidin molecule as a starting model and the final models of avidin/B9P and avidin/D9P were refined to resolutions of 2.0 Å and 2.1 Å, respectively. Our data reveal changes in loop conformation as well as in overall fold and quaternary arrangement of the avidin upon the binding of these fluorescent probes. Moreover, the crystal structures allowed analysis of the details of the interactions between the protein and the pyrene derivatives. Structural description of the complexes will contribute to the design of conjugates for expanding the capabilities of avidin–biotin technology. Full article

(This article belongs to the Section Bioorganic Chemistry)

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12 pages, 2770 KiB

Open AccessArticle

Nanoemulsion Formulations of Fungicide Tebuconazole for Agricultural Applications

by Vianney Díaz-Blancas¹, Dora I. Medina², Erika Padilla-Ortega^1,*

, Raquel Bortolini-Zavala¹, Melissa Olvera-Romero¹ and Gabriel Luna-Bárcenas^1,*

¹ Cinvestav Queretaro, Libramiento Norponiente 2000, Fracc. Real de Juriquilla, Queretaro, Queretaro 76230, Mexico

² Tecnologico de Monterrey, School of Engineering and Sciences, Atizapan de Zaragoza, Estado de Mexico 52926, Mexico

Molecules 2016, 21(10), 1271; https://doi.org/10.3390/molecules21101271 - 26 Sep 2016

Cited by 56 | Viewed by 8317

Abstract

Tebuconazole (TBZ) nanoemulsions (NEs) were formulated using a low energy method. TBZ composition directly affected the drop size and surface tension of the NE. Water fraction and the organic-to-surfactant-ratio (R_O/S) were evaluated in the range of 1–90 and 1–10 wt %, [...] Read more.

Tebuconazole (TBZ) nanoemulsions (NEs) were formulated using a low energy method. TBZ composition directly affected the drop size and surface tension of the NE. Water fraction and the organic-to-surfactant-ratio (R_O/S) were evaluated in the range of 1–90 and 1–10 wt %, respectively. The study was carried out with an organic phase (OP) consisting of an acetone/glycerol mixture containing TBZ at a concentration of 5.4 wt % and Tween 80 (TW80) as a nonionic and Agnique BL1754 (AG54) as a mixture of nonionic and anionic surfactants. The process involved a large dilution of a bicontinuous microemulsion (ME) into an aqueous phase (AP). Pseudo-ternary phase diagrams of the OP//TW80//AP and OP//AG54//AP systems at T = 25 °C were determined to map ME regions; these were in the range of 0.49–0.90, 0.01–0.23, and 0.07–0.49 of OP, AP, and surfactant, respectively. Optical microscope images helped confirm ME formation and system viscosity was measured in the range of 25–147 cP. NEs with drop sizes about 9 nm and 250 nm were achieved with TW80 and AG54, respectively. An innovative low-energy method was used to develop nanopesticide TBZ formulations based on nanoemulsion (NE) technology. The surface tension of the studied systems can be lowered 50% more than that of pure water. This study’s proposed low-energy NE formulations may prove useful in sustainable agriculture. Full article

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9 pages, 1933 KiB

Open AccessArticle

Enhanced Cellular Uptake and Pharmacokinetic Characteristics of Doxorubicin-Valine Amide Prodrug

by Yohan Park¹, Ju-Hwan Park², Suryeon Park¹, Song Yi Lee³, Kwan Hyung Cho¹, Dae-Duk Kim²

, Won-Sik Shim⁴, In-Soo Yoon⁵, Hyun-Jong Cho^3,* and Han-Joo Maeng^4,*

¹ College of Pharmacy, Inje University, Gyeongnam 50834, Korea

² College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 08826, Korea

³ College of Pharmacy, Kangwon National University, Gangwon 24341, Korea

⁴ College of Pharmacy, Gachon University, Incheon 21936, Korea

⁵ College of Pharmacy and Natural Medicine Research Institute, Mokpo National University, Jeonnam 58554, Korea

Molecules 2016, 21(10), 1272; https://doi.org/10.3390/molecules21101272 - 22 Sep 2016

Cited by 11 | Viewed by 6641

Abstract

In this study, we synthesized the valine (Val)-conjugated amide prodrug of doxorubicin (DOX) by the formation of amide bonds between DOX and Val. The synthesis of the DOX-Val prodrug was identified by a proton nuclear magnetic resonance (¹H-NMR) assay. In the [...] Read more.

In this study, we synthesized the valine (Val)-conjugated amide prodrug of doxorubicin (DOX) by the formation of amide bonds between DOX and Val. The synthesis of the DOX-Val prodrug was identified by a proton nuclear magnetic resonance (¹H-NMR) assay. In the MCF-7 cells (human breast adenocarcinoma cell; amino acid transporter–positive cell), the cellular accumulation efficiency of DOX-Val was higher than that of DOX according to the flow cytometry analysis data. Using confocal laser scanning microscopy (CLSM) imaging, it was confirmed that DOX-Val as well as DOX was mainly distributed in the nucleus of cancer cells. DOX-Val was intravenously administered to rats at a dose of 4 mg/kg, and the plasma concentrations of DOX-Val (prodrug) and DOX (formed metabolite) were quantitatively determined. Based on the systemic exposure (represented as area under the curve (AUC) values) of DOX-Val (prodrug) and DOX (formed metabolite), approximately half of DOX-Val seemed to be metabolized into DOX. However, it is expected that the remaining DOX-Val may exert improved cellular uptake efficiency in cancer cells after its delivery to the cancer region. Full article

(This article belongs to the Section Medicinal Chemistry)

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11 pages, 2726 KiB

Open AccessReview

Anti-Inflammatory Activity of Citrus bergamia Derivatives: Where Do We Stand?

by Nadia Ferlazzo¹, Santa Cirmi¹

, Gioacchino Calapai², Elvira Ventura-Spagnolo³, Sebastiano Gangemi^4,5 and Michele Navarra^1,*

¹ Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Messina I-98168, Italy

² Department of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina, Messina I-98125, Italy

³ Department of Biotechnology and Legal Medicine, University of Palermo, Palermo I-90127, Italy

⁴ Department of Clinical and Experimental Medicine, University of Messina, Messina I-98125, Italy

⁵ Institute of Applied Sciences and Intelligent Systems (ISASI), National Research Council (CNR), Pozzuoli I-80078, Italy

Molecules 2016, 21(10), 1273; https://doi.org/10.3390/molecules21101273 - 23 Sep 2016

Cited by 65 | Viewed by 8606

Abstract

Inflammatory diseases affect a large portion of the worldwide population, and chronic inflammation is a major risk factor for several dangerous pathologies. To limit the side effects of both synthetic and biological anti-inflammatory drugs, the use of herbal medicines, nutraceuticals and food supplements [...] Read more.

Inflammatory diseases affect a large portion of the worldwide population, and chronic inflammation is a major risk factor for several dangerous pathologies. To limit the side effects of both synthetic and biological anti-inflammatory drugs, the use of herbal medicines, nutraceuticals and food supplements has increased tremendously as alternative and/or complementary medicine to treat several pathologies, including inflammation. During the last decades, the biological properties of Citrus bergamia (bergamot) derivatives have obtained important scientific achievements, and it has been suggested their use in a context of a multitarget pharmacological strategy. Here, we present an overview of the anti-inflammatory properties of bergamot extracts that could represent the scientific basis for develop novel and alternative strategies to improve health status and attenuate inflammatory conditions. Full article

(This article belongs to the Special Issue Natural Products and Inflammation)

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25 pages, 1815 KiB

Open AccessArticle

The Structure–Antimicrobial Activity Relationships of a Promising Class of the Compounds Containing the N-Arylpiperazine Scaffold

by Ivan Malík^1,*, Jozef Csöllei², Josef Jampílek¹

, Lukáš Stanzel¹, Iveta Zadražilová³, Jan Hošek⁴

, Šárka Pospíšilová³, Alois Čížek³, Aidan Coffey⁵

and Jim O’Mahony⁵

¹ Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Comenius University in Bratislava, Odbojárov 10, Bratislava SK-832 32, Slovak Republic

² Department of Chemical Drugs, Faculty of Pharmacy, University of Veterinary and Pharmaceutical Sciences in Brno, Palackého 1946/1, Brno CZ-612 42, Czech Republic

³ Department of Infectious Diseases and Microbiology, Faculty of Veterinary Medicine, University of Veterinary and Pharmaceutical Sciences in Brno, Palackého 1946/1, Brno CZ-612 42, Czech Republic

⁴ Department of Molecular Biology and Pharmaceutical Biotechnology, Faculty of Pharmacy, University of Veterinary and Pharmaceutical Sciences in Brno, Palackého 1946/1, Brno CZ-612 42, Czech Republic

⁵ Department of Biological Sciences, Cork Institute of Technology, Bishopstown, Cork T12 P928, Ireland

Molecules 2016, 21(10), 1274; https://doi.org/10.3390/molecules21101274 - 26 Sep 2016

Cited by 17 | Viewed by 6670

Abstract

This research was focused on in silico characterization and in vitro biological testing of the series of the compounds carrying a N-arylpiperazine moiety. The in silico investigation was based on the prediction of electronic, steric and lipohydrophilic features. The molecules were screened [...] Read more.

This research was focused on in silico characterization and in vitro biological testing of the series of the compounds carrying a N-arylpiperazine moiety. The in silico investigation was based on the prediction of electronic, steric and lipohydrophilic features. The molecules were screened against Mycobacterium avium subsp. paratuberculosis CIT03, M. smegmatis ATCC 700084, M. kansasii DSM 44162, M. marinum CAMP 5644, Staphylococcus aureus ATCC 29213, methicillin-resistant S. aureus 63718, Escherichia coli ATCC 25922, Enterococcus faecalis ATCC 29212, Candida albicans CCM 8261, C. parapsilosis CCM 8260 and C. krusei CCM 8271, respectively, by standardized microdilution methods. The eventual antiproliferative (cytotoxic) impact of those compounds was examined on a human monocytic leukemia THP-1 cell line, as a part of the biological study. Promising potential against M. kansasii was found for 1-[3-(3-ethoxyphenylcarbamoyl)oxy-2-hydroxypropyl]-4-(3-trifluoromethylphenyl)piperazin-1-ium chloride (MIC = 31.75 μM), which was comparable to the activity of isoniazid (INH; MIC = 29.17 μM). Moreover, 1-{2-hydroxy-3-(3-methoxyphenylcarbamoyl)oxy)propyl}-4-(4-fluorophenyl)piperazin-1-ium chloride was even more effective (MIC = 17.62 μM) against given mycobacterium. Among the tested N-arylpiperazines, 1-{2-hydroxy-3-(4-methoxyphenylcarbamoyl)oxy)propyl}-4-(3-trifluorometh-ylphenyl)piperazin-1-ium chloride was the most efficient against M. marinum (MIC = 65.32 μM). One of the common features of all investigated substances was their insignificant antiproliferative (i.e., non-cytotoxic) effect. The study discussed structure–antimicrobial activity relationships considering electronic, steric and lipophilic properties. Full article

(This article belongs to the Special Issue Selected Papers from the 8th Central European Conference ‘Chemistry towards Biology’ (CTB-2016))

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14 pages, 1748 KiB

Open AccessArticle

Analysis of Flavonoids in Rhamnus davurica and Its Antiproliferative Activities

by Guilin Chen^1,2, Xun Li^1,2, Flora Saleri^1,2 and Mingquan Guo^1,3,*

¹ Key Laboratory of Plant Germplasm Enhancement and Specialty Agriculture, Wuhan Botanical Garden, Chinese Academy of Sciences, Wuhan 430074, China

² Graduate University of Chinese Academy of Sciences, Beijing 100049, China

³ Sino-Africa Joint Research Center, Chinese Academy of Sciences, Wuhan 430074, China

Molecules 2016, 21(10), 1275; https://doi.org/10.3390/molecules21101275 - 23 Sep 2016

Cited by 139 | Viewed by 9790

Abstract

Rhamnus davurica Pall. (R. davurica) has been used as a traditional medicinal herb for many years in China and abroad. It has been well documented as a rich source of flavonoids with diversified structures, which in turn results in far-ranging biological [...] Read more.

Rhamnus davurica Pall. (R. davurica) has been used as a traditional medicinal herb for many years in China and abroad. It has been well documented as a rich source of flavonoids with diversified structures, which in turn results in far-ranging biological activities, such as anti-inflammation, anticancer, antibacterial and antioxidant activities. In order to further correlate their anticancer potentials with the phytochemical components, the fingerprint profile of R. davurica herb from Dongbei was firstly investigated using HPLC-ESI-MS/MS. Thirty two peaks were detected and identified, 14 of which were found in R. davurica for the first time in this work. Furthermore, a total of 23 peaks were resolved as flavonoids, which are the major components found in R. davurica. Meanwhile, the antiproliferative activities against human cancer cells of HT-29 and SGC-7901 in vitro exhibited distinct inhibitory effects with IC₅₀ values at 24.96 ± 0.74 and 89.53 ± 4.11 μg/mL, respectively. Finally, the general toxicity against L-O2 cells displayed a much higher IC₅₀ at 229.19 ± 8.52 μg/mL, which suggested very low or no toxicity on hepatic cell viability. The current study revealed for the first time the correlations between the flavonoids of R. davurica with their antiproliferative activities, which indicated that the fingerprint profile of flavonoids and their anticancer activities could provide valuable information on the quality control for herbal medicines and their derived natural remedies from this valuable medicinal plant. Full article

(This article belongs to the Special Issue Flavonoids: From Structure to Health Issues)

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10 pages, 389 KiB

Open AccessArticle

Identification of Nematicidal Constituents of Notopterygium incisum Rhizomes against Bursaphelenchus xylophilus and Meloidogyne incognita

by Gai Liu¹, Daowan Lai²

, Qi Zhi Liu¹, Ligang Zhou²

and Zhi Long Liu^1,*

¹ Department of Entomology, China Agricultural University, Haidian District, Beijing 100193, China

² Department of Plant Pathology, China Agricultural University, Haidian District, Beijing 100193, China

Molecules 2016, 21(10), 1276; https://doi.org/10.3390/molecules21101276 - 23 Sep 2016

Cited by 47 | Viewed by 6897

Abstract

During a screening program for new agrochemicals from Chinese medicinal herbs, the ethanol extract of Notopterygium incisum rhizomes was found to possess strong nematicidal activity against the two species of nematodes, Bursaphelenchus xylophilus and Meloidogyne incognita. Based on bioactivity-guided fractionation, the four [...] Read more.

During a screening program for new agrochemicals from Chinese medicinal herbs, the ethanol extract of Notopterygium incisum rhizomes was found to possess strong nematicidal activity against the two species of nematodes, Bursaphelenchus xylophilus and Meloidogyne incognita. Based on bioactivity-guided fractionation, the four constituents were isolated from the ethanol extract and identified as columbianetin, falcarindiol, falcarinol, and isoimperatorin. Among the four isolated constituents, two acetylenic compounds, falcarindiol and falcarinol (2.20–12.60 μg/mL and 1.06–4.96 μg/mL, respectively) exhibited stronger nematicidal activity than two furanocoumarins, columbianetin, and isoimperatorin (21.83–103.44 μg/mL and 17.21–30.91 μg/mL, respectively) against the two species of nematodes, B. xylophilus and M. incognita. The four isolated constituents also displayed phototoxic activity against the nematodes. The results indicate that the ethanol extract of N. incisum and its four isolated constituents have potential for development into natural nematicides for control of plant-parasitic nematodes. Full article

(This article belongs to the Section Natural Products Chemistry)

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8 pages, 2097 KiB

Open AccessArticle

Theoretical Study on Regioselectivity of the Diels-Alder Reaction between 1,8-Dichloroanthracene and Acrolein

by Mujeeb A. Sultan^1,*, Usama Karama¹, Abdulrahman I. Almansour¹ and Saied M. Soliman^2,3,*

¹ Chemistry Department, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia

² Department of Chemistry, Rabigh College of Science and Art, P.O. Box 344, Rabigh 21911, Saudi Arabia

³ Department of Chemistry, Faculty of Science, Alexandria University, P.O. Box 426, Ibrahimia, Alexandria 21321, Egypt

Molecules 2016, 21(10), 1277; https://doi.org/10.3390/molecules21101277 - 23 Sep 2016

Cited by 8 | Viewed by 6888

Abstract

A theoretical study of the regioselectivity of the Diels-Alder reaction between 1,8-dichloroanthracene and acrolein is performed using DFT at the B3LYP/6-31G(d,p) level of theory. The FMO analysis, global and local reactivity indices confirmed the reported experimental results. Potential energy surface analysis showed that [...] Read more.

A theoretical study of the regioselectivity of the Diels-Alder reaction between 1,8-dichloroanthracene and acrolein is performed using DFT at the B3LYP/6-31G(d,p) level of theory. The FMO analysis, global and local reactivity indices confirmed the reported experimental results. Potential energy surface analysis showed that the cycloadditions (CAs) favor the formation of the anti product. These results are in good agreement with the reported results obtained experimentally where the anti is the major product. Full article

(This article belongs to the Special Issue Density Functional Theory and Reactivity Indices: Applications in Organic Chemical Reactivity)

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19 pages, 1096 KiB

Open AccessReview

Potential of Natural Products in the Inhibition of Adipogenesis through Regulation of PPARγ Expression and/or Its Transcriptional Activity

by Shi Feng, Laura Reuss and Yu Wang^*

Citrus Research and Education Center, Food Science and Human Nutrition, University of Florida, 700 Experiment Station Road, Lake Alfred, FL 33850, USA

Molecules 2016, 21(10), 1278; https://doi.org/10.3390/molecules21101278 - 23 Sep 2016

Cited by 94 | Viewed by 12202

Abstract

Obesity is a global health problem characterized as an increase in the mass of adipose tissue. Adipogenesis is one of the key pathways that increases the mass of adipose tissue, by which preadipocytes mature into adipocytes through cell differentiation. Peroxisome proliferator-activated receptor γ [...] Read more.

Obesity is a global health problem characterized as an increase in the mass of adipose tissue. Adipogenesis is one of the key pathways that increases the mass of adipose tissue, by which preadipocytes mature into adipocytes through cell differentiation. Peroxisome proliferator-activated receptor γ (PPARγ), the chief regulator of adipogenesis, has been acutely investigated as a molecular target for natural products in the development of anti-obesity treatments. In this review, the regulation of PPARγ expression by natural products through inhibition of CCAAT/enhancer-binding protein β (C/EBPβ) and the farnesoid X receptor (FXR), increased expression of GATA-2 and GATA-3 and activation of the Wnt/β-catenin pathway were analyzed. Furthermore, the regulation of PPARγ transcriptional activity associated with natural products through the antagonism of PPARγ and activation of Sirtuin 1 (Sirt1) and AMP-activated protein kinase (AMPK) were discussed. Lastly, regulation of mitogen-activated protein kinase (MAPK) by natural products, which might regulate both PPARγ expression and PPARγ transcriptional activity, was summarized. Understanding the role natural products play, as well as the mechanisms behind their regulation of PPARγ activity is critical for future research into their therapeutic potential for fighting obesity. Full article

(This article belongs to the Special Issue Natural Products in Anti-Obesity Therapy)

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11 pages, 1767 KiB

Open AccessArticle

Development of an Innovative Intradermal siRNA Delivery System Using a Combination of a Functional Stearylated Cytoplasm-Responsive Peptide and a Tight Junction-Opening Peptide

by Hisako Ibaraki^†, Takanori Kanazawa^*,†, Yuuki Takashima, Hiroaki Okada and Yasuo Seta

Laboratory of Pharmaceutics and Drug Delivery, Department of Pharmaceutical Science, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan

Molecules 2016, 21(10), 1279; https://doi.org/10.3390/molecules21101279 - 24 Sep 2016

Cited by 21 | Viewed by 6755

Abstract

As a new category of therapeutics for skin diseases including atopic dermatitis (AD), nucleic acids are gaining importance in the clinical setting. Intradermal administration is noninvasive and improves patients′ quality of life. However, intradermal small interfering RNA (siRNA) delivery is difficult because of [...] Read more.

As a new category of therapeutics for skin diseases including atopic dermatitis (AD), nucleic acids are gaining importance in the clinical setting. Intradermal administration is noninvasive and improves patients′ quality of life. However, intradermal small interfering RNA (siRNA) delivery is difficult because of two barriers encountered in the skin: intercellular lipids in the stratum corneum and tight junctions in the stratum granulosum. Tight junctions are the major barrier in AD; therefore, we focused on functional peptides to devise an intradermal siRNA delivery system for topical skin application. In this study, we examined intradermal siRNA permeability in the tape-stripped (20 times) back skin of mice or AD-like skin of auricles treated with 6-carboxyfluorescein-aminohexyl phosphoramidite (FAM)-labeled siRNA, the tight junction modulator AT1002, and the functional cytoplasm-responsive stearylated peptide STR-CH₂R₄H₂C by using confocal laser microscopy. We found that strong fluorescence was observed deep and wide in the epidermis and dermis of back skin and AD-like ears after siRNA with STR-CH₂R₄H₂C and AT1002 treatment. After 10 h from administration, brightness of FAM-siRNA was significantly higher for STR-CH₂R₄H₂C + AT1002, compared to other groups. In addition, we confirmed the nontoxicity of STR-CH₂R₄H₂C as a siRNA carrier using PAM212 cells. Thus, our results demonstrate the applicability of the combination of STR-CH₂R₄H₂C and AT1002 for effective intradermal siRNA delivery. Full article

(This article belongs to the Special Issue Nucleic Acid-based Drug)

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9 pages, 915 KiB

Open AccessArticle

Cytoproliferative and Cytoprotective Effects of Striatisporolide A Isolated from Rhizomes of Athyrium multidentatum (Doell.) Ching on Human Umbilical Vein Endothelial Cells

by Dong-Mei Liu^1,†, Ji-Wen Sheng^1,*,†, Si-Hong Wang²

, Wei-Fen Zhang¹, Wei Zhang³ and Dai-Juan Zhang¹

¹ Department of Pharmacy, Weifang Medical University, Weifang 261053, China

² Analysis and Test Center, Yianbian University, Yanji 133002, China

³ Plastic Surgery Institute of Weifang Medical University, Weifang 261053, China

Molecules 2016, 21(10), 1280; https://doi.org/10.3390/molecules21101280 - 24 Sep 2016

Cited by 10 | Viewed by 4612

Abstract

Objectives: The aim of this study was to investigate the proliferative and protective effects of striatisporolide A (SA) obtained from the rhizomes of Athyrium multidentatum (Doell.) Ching on human umbilical vein endothelial cells (HUVECs). Methods: Cell viability was measured by the [...] Read more.

Objectives: The aim of this study was to investigate the proliferative and protective effects of striatisporolide A (SA) obtained from the rhizomes of Athyrium multidentatum (Doell.) Ching on human umbilical vein endothelial cells (HUVECs). Methods: Cell viability was measured by the MTT method. Cell apoptosis was determined by flow cytometry. Intracellular ROS was measured by the 2,7-dichlorodihydrofluorescein diacetate (DCFH-DA) fluorescent probe. Results: The viability rate in cells treated with 100 µM SA alone was increased to 128.72% ± 0.19% and showed a significant difference compared with the control group (p < 0.05). Meanwhile, SA augmented the cell viabilities in H₂O₂-treated HUVECs, and the cell viability was enhanced to 56.94% ± 0.13% (p < 0.01) when pre-incubated with 50 µM SA. The cell apoptosis rates were reduced to 2.17% ± 0.20% (p < 0.05) and 3.1% ± 0.34% (p < 0.01), respectively, after treatment with SA alone or SA/H₂O₂. SA inhibited the overproduction of reactive oxygen species (ROS) in HUVECs induced by H₂O₂ and the fluorescent intensity was abated to 9.47 ± 0.61 after pre-incubated with 100 μM SA. Conclusions: The biological activities of SA were explored for the first time. Our results stated that SA exhibited significant cytoproliferative and minor cytoprotective effects on HUVECs. We presume that the mechanisms of the proliferation and protection actions of SA involve interference with the generation of ROS and the cell apoptosis. These findings provide a new perspective on the biological potential of butenolides. Full article

(This article belongs to the Section Natural Products Chemistry)

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15 pages, 3448 KiB

Open AccessArticle

Nanostructured Samarium Doped Fluorapatites and Their Catalytic Activity towards Synthesis of 1,2,4-Triazoles

by Kranthi Kumar Gangu, Suresh Maddila, Surya Narayana Maddila and Sreekantha B. Jonnalagadda^*

School of Chemistry & Physics, University of KwaZulu-Natal, Westville Campus, Chiltern Hills, Durban-4000, South Africa

Molecules 2016, 21(10), 1281; https://doi.org/10.3390/molecules21101281 - 24 Sep 2016

Cited by 29 | Viewed by 5992

Abstract

An investigation was conducted into the influence of the amino acids as organic modifiers in the facile synthesis of metal incorporated fluorapatites (FAp) and their properties. The nanostructured Sm doped fluorapatites (Sm-FAp) were prepared by a co-precipitation method using four different amino acids, [...] Read more.

An investigation was conducted into the influence of the amino acids as organic modifiers in the facile synthesis of metal incorporated fluorapatites (FAp) and their properties. The nanostructured Sm doped fluorapatites (Sm-FAp) were prepared by a co-precipitation method using four different amino acids, namely glutamic acid, aspartic acid, glycine and histidine. The materials were characterized by various techniques including X-ray diffraction (XRD), Fourier transform infra-red spectroscopy (FT-IR), field emission scanning electron microscopy (FE-SEM), energy-dispersive X-ray spectroscopy (EDX), high resolution transmission electron microscopy (HR-TEM), N₂-adsorption/desorption isotherm, temperature programmed desorption (TPD) and fluorescence spectrophotometry. Under similar conditions, Sm-FAp prepared using different amino acids exhibited distinctly different morphological structures, surface area and pore properties. Their activity as catalysts was assessed and Sm-FAp/Glycine displayed excellent efficiency in the synthesis of 1,2,4-triazole catalyzing the reaction between 2-nitrobenzaldehyde and thiosemicarbazide with exceptional selectivity and 98% yield in a short time interval (10 min). The study provides an insight into the role of organic modifiers as controllers of nucleation, growth and aggregation which significantly influence the nature and activity of the catalytic sites on Sm-FAp. Sm-FAp could also have potential as photoactive material. Full article

(This article belongs to the Section Organometallic Chemistry)

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8 pages, 1075 KiB

Open AccessArticle

Novel Diterpenoids from the Twigs of Podocarpus nagi

by Yuan-Dong Zheng^1,2,3,†, Xing-Chen Guan^4,†, Dan Li⁵, An-Qi Wang⁵, Chang-Qiang Ke^1,2, Chun- Ping Tang^1,2, Li-Gen Lin⁵

, Yang Ye^1,2,3, Zheng-Liang Wang^4,* and Sheng Yao^1,2,*

¹ State Key Laboratory of Drug Research & Natural Products Chemistry Department, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China

² University of Chinese Academy of Sciences, Beijing 100049, China

³ School of Life Science and Technology, ShanghaiTech University, Shanghai 201203, China

⁴ School of Chemistry & Environmental Engineering, Yangtze University, Jingzhou 434023, China

⁵ State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau 999078, China

Molecules 2016, 21(10), 1282; https://doi.org/10.3390/molecules21101282 - 25 Sep 2016

Cited by 33 | Viewed by 5977

Abstract

Phytochemical investigation of the twigs of Podocarpus nagi (Podocarpaceae) led to the isolation of two new abietane-type diterpenoids, named 1β,16-dihydroxylambertic acid (1) and 3β,16-dihydroxylambertic acid (2), along with two new ent-pimarane-type diterpenoids, named ent-2β,15,16,18-tetrahydroxypimar-8(14)-ene (3) [...] Read more.

Phytochemical investigation of the twigs of Podocarpus nagi (Podocarpaceae) led to the isolation of two new abietane-type diterpenoids, named 1β,16-dihydroxylambertic acid (1) and 3β,16-dihydroxylambertic acid (2), along with two new ent-pimarane-type diterpenoids, named ent-2β,15,16,18-tetrahydroxypimar-8(14)-ene (3) and ent-15-oxo-2β,16,18-trihydroxypimar-8(14)-ene (4). Their respective structures were elucidated on the basis of spectroscopic analyses, including 1D- and 2D-NMR, IR, CD, and HR-ESI-MS. This is the first time ent-pimarane-type diterpenoids from the genus Podocarpus has been reported. All four new compounds were tested for cytotoxic activity. The MTT assay results showed that compounds 3 and 4 significantly inhibited the proliferation of human cervical cancer Hela cells, human lung cancer A549 cells, and human breast cancer MCF-7 cells at a concentration of 10 μM. Furthermore, using the lipopolysaccharide (LPS)-stimulated RAW264.7 cells, compounds 2 and 4 were found to significantly inhibit nitrogen oxide (NO) production with IC50 values of 26.5 ± 6.1 and 17.1 ± 1.5 μM, respectively. Full article

(This article belongs to the Section Natural Products Chemistry)

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12 pages, 1008 KiB

Open AccessArticle

Terminamines K–S, Antimetastatic Pregnane Alkaloids from the Whole Herb of Pachysandra terminalis

by Xiang-Yu Li, Yang Yu, Miao Jia, Mei-Na Jin, Nan Qin, Chuan Zhao^* and Hong-Quan Duan^*

Tianjin Key Laboratory on Technologies Enabling Development Clinical Therapeutics and Diagnostics (Theranostics), School of Pharmacy, Research Center of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China

Molecules 2016, 21(10), 1283; https://doi.org/10.3390/molecules21101283 - 26 Sep 2016

Cited by 9 | Viewed by 4514

Abstract

Nine new pregnane alkaloids (1–9), together with eight known alkaloids (10–17), were isolated from the whole herb of Pachysandra terminalis. Their structures were elucidated on the basis of spectroscopic analyses. In addition, the isolates [...] Read more.

Nine new pregnane alkaloids (1–9), together with eight known alkaloids (10–17), were isolated from the whole herb of Pachysandra terminalis. Their structures were elucidated on the basis of spectroscopic analyses. In addition, the isolates were examined for their ability to inhibit the migration of MDA-MB-231 cells induced by the chemokine epidermal growth factor (EGF). Alkaloids 1, 5, 7, 9, 12, and 17 presented significant anti-metastasis activities compared with the positive reagent, LY294002. Full article

(This article belongs to the Section Natural Products Chemistry)

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13 pages, 3458 KiB

Open AccessArticle

Improvement of Peptide-Based Tumor Immunotherapy Using pH-Sensitive Fusogenic Polymer-Modified Liposomes

by Yuta Yoshizaki¹, Eiji Yuba¹

, Toshihiro Komatsu², Keiko Udaka², Atsushi Harada¹ and Kenji Kono^1,*

¹ Department of Applied Chemistry, Graduate School of Engineering, Osaka Prefecture University, 1-1 Gakuen-cho, Naka-ku, Sakai, Osaka 599-8531, Japan

² Department of Immunology, School of Medicine, Kochi University, Kohasu, Okou-cho, Nankoku, Kochi 783-8505, Japan

Molecules 2016, 21(10), 1284; https://doi.org/10.3390/molecules21101284 - 26 Sep 2016

Cited by 42 | Viewed by 7461

Abstract

To establish peptide vaccine-based cancer immunotherapy, we investigated the improvement of antigenic peptides by encapsulation with pH-sensitive fusogenic polymer-modified liposomes for induction of antigen-specific immunity. The liposomes were prepared by modification of egg yolk phosphatidylcholine and l-dioleoyl phosphatidylethanolamine with 3-methyl-glutarylated hyperbranched poly(glycidol) [...] Read more.

To establish peptide vaccine-based cancer immunotherapy, we investigated the improvement of antigenic peptides by encapsulation with pH-sensitive fusogenic polymer-modified liposomes for induction of antigen-specific immunity. The liposomes were prepared by modification of egg yolk phosphatidylcholine and l-dioleoyl phosphatidylethanolamine with 3-methyl-glutarylated hyperbranched poly(glycidol) (MGlu-HPG) and were loaded with antigenic peptides derived from ovalbumin (OVA) OVA-I (SIINFEKL), and OVA-II (PSISQAVHAAHAEINEAP_βA), which bind, respectively, to major histocompatibility complex (MHC) class I and class II molecules on dendritic cell (DCs). The peptide-loaded liposomes were taken up efficiently by DCs. The peptides were delivered into their cytosol. Administration of OVA-I-loaded MGlu-HPG-modified liposomes to mice bearing OVA-expressing E.G7-OVA tumors induced the activation of OVA-specific CTLs much more efficiently than the administration of free OVA-I peptide did. Mice strongly rejected E.G7-OVA cells after immunization with OVA-I peptide-loaded MGlu-HPG liposomes, although mice treated with free OVA-I peptide only slightly rejected the cells. Furthermore, efficient suppression of tumor volume was observed when tumor-bearing mice were immunized with OVA-I-peptide-loaded liposomes. Immunization with OVA-II-loaded MGlu-HPG-modified liposomes exhibited much lower tumor-suppressive effects. Results indicate that MGlu-HPG liposomes might be useful for improvement of CTL-inducing peptides for efficient cancer immunotherapy. Full article

(This article belongs to the Special Issue Stimuli-Responsive Biomaterials in Biomedical Applications)

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11 pages, 9273 KiB

Open AccessArticle

Acacetin Protects Mice from Staphylococcus aureus Bloodstream Infection by Inhibiting the Activity of Sortase A

by Chongwei Bi^1,†, Xiaoyun Dong^2,†, Xiaobo Zhong¹, Hongjun Cai³, Dacheng Wang^1,* and Lin Wang^4,*

¹ College of Animal Science, Jilin University, Changchun 130062, China

² Department of Pharmacology, College of Basic Medical Science, Jilin University, Changchun 130062, China

³ College of Animal Science and Technology, Jilin Agricultural University, Changchun 130062, China

⁴ Key Laboratory of Zoonosis Research, Ministry of Education/Institute of Zoonosis/College of Veterinary Medicine, Jilin University, Changchun 130062, China

Molecules 2016, 21(10), 1285; https://doi.org/10.3390/molecules21101285 - 26 Sep 2016

Cited by 30 | Viewed by 5750

Abstract

Staphylococcus aureus (S. aureus) is a major cause of infection in hospitals and communities. Widespread dissemination of multi-drug resistant S. aureus is a serious threat to the health of humans and animals. An anti-virulence strategy has been widely considered as an [...] Read more.

Staphylococcus aureus (S. aureus) is a major cause of infection in hospitals and communities. Widespread dissemination of multi-drug resistant S. aureus is a serious threat to the health of humans and animals. An anti-virulence strategy has been widely considered as an alternative therapeutic approach. Inhibitors of virulence factors are able to treat S. aureus infections without influencing the growth or viability of bacteria and rarely lead to bacterial resistance. Sortase A (SrtA) is a membrane-associated cysteine transpeptidase that catalyzes up to 25 surface proteins that covalently bind to cell wall peptidoglycans. In S. aureus, most of these surface proteins have been identified as important virulence factors that are vital in bacterial pathogenesis. In the present study, we show that acacetin, a natural flavonoid compound, inhibits the activity of SrtA in S. aureus (IC₅₀ = 36.46 ± 4.69 μg/mL, 128 μM) which affects the assembly of protein A (SpA) to cell walls and reduces the binding of S. aureus to fibrinogen (Fg). The mechanism of the interaction between acacetin and SrtA were preliminarily discussed using molecular dynamics simulations. The results suggested that acacetin adopted a compact conformation binding at the pocket of the SrtA via residues Arg-139 and Lys-140. By performing an animal infection model, we demonstrated that acacetin was able to protect mice from renal abscess formation induced by S. aureus and significantly increased survival rates. Taken together, these findings suggest that acacetin may be a promising candidate for the development of anti-S. aureus drugs. Full article

(This article belongs to the Section Medicinal Chemistry)

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10 pages, 2922 KiB

Open AccessArticle

Anti-Cancer Effect of Quercetin in Xenograft Models with EBV-Associated Human Gastric Carcinoma

by Hwan Hee Lee^1,2, Seulki Lee^1,2, Yu Su Shin³, Miyeon Cho⁴

, Hyojeung Kang^4,* and Hyosun Cho^1,2,*

¹ College of Pharmacy, Duksung Women’s University, Seoul 132-714, Korea

² Innovative Drug Center, Duksung Women’s University, Seoul 132-714, Korea

³ Department of Medicinal Crop Research, National Institute of Horticultural and Herbal Science, Rural Development Administration, Eumseong 369-873, Korea

⁴ College of Pharmacy, Research Institute of Pharmaceutical Sciences and Institute for Microorganisms, Kyungpook National University, Daegu 702-701, Korea

Molecules 2016, 21(10), 1286; https://doi.org/10.3390/molecules21101286 - 26 Sep 2016

Cited by 42 | Viewed by 9268

Abstract

Licorice extracts have been widely used in herbal and folk medications. Glycyrrhiza contains diverse range of biological compounds including triterpenes (glycyrrhizin, glycyrrhizic acid) and flavonoids (quercetin, liquiritin, liquiritigenin, glabridin, licoricidin, isoliquiritigenin). The flavonoids in licorice are known to have strong anti-cancer activities. Quercetin, [...] Read more.

Licorice extracts have been widely used in herbal and folk medications. Glycyrrhiza contains diverse range of biological compounds including triterpenes (glycyrrhizin, glycyrrhizic acid) and flavonoids (quercetin, liquiritin, liquiritigenin, glabridin, licoricidin, isoliquiritigenin). The flavonoids in licorice are known to have strong anti-cancer activities. Quercetin, the most abundant flavonoid, has been shown to have anti-ulcer, anti-cancer, antioxidant, and anti-inflammatory properties. Latent Epstein-Barr virus (EBV) infection can lead to serious malignancies, such as, Burkitt’s lymphoma, Hodgkin’s disease and gastric carcinoma(GC), and (Epstein-Barr virus associated gastric carcinoma) EBVaGC is one of the most common EBV-associated cancers. In this study, the authors first examined the anti-cancer effects of quercetin and isoliquiritigenin in vivo xenograft animal models implanted with EBV(+) human gastric carcinoma (SNU719) or EBV(−) human gastric carcinoma (MKN74), and then explored the molecular mechanisms responsible for their anti-cancer activities. The results obtained showed that anti-cancer effect of quercetin was greater than isoliquiritigenin in mice injected with EBV(+) human gastric carcinoma (SNU719) cells. On the other hand, quercetin and isoliquiritigenin had similar anti-cancer effects in mice injected with EBV(−) human gastric carcinoma (MKN74) cells. Interestingly, quercetin inhibited EBV viral protein expressions, including EBNA-1 and LMP-2 proteins in tumor tissues from mice injected with EBV(+) human gastric carcinoma. Quercetin more effectively induced p53-dependent apoptosis than isoliquiritigenin in EBV(+) human gastric carcinoma, and this induction was correlated with increased expressions of the cleaved forms of caspase-3, -9, and Parp. In EBV(−)human gastric carcinoma (MKN74), both quercetin and isoliquiritigenin induced the expressions of p53, Bax, and Puma and the cleaved forms of caspase-3 and -9 and Parp at similar levels. Full article

(This article belongs to the Collection Efficient Pharmaceutical and Chemical Approaches for Anticancer Therapy: Design, Preliminary Evaluations, and Further Developments)

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10 pages, 407 KiB

Open AccessArticle

Antiprotozoal and Antiglycation Activities of Sesquiterpene Coumarins from Ferula narthex Exudate

by Adnan Amin¹, Emmy Tuenter¹, Paul Cos²

, Louis Maes²

, Vassiliki Exarchou¹, Sandra Apers¹ and Luc Pieters^1,*

¹ Natural Products & Food Research and Analysis (NatuRA), Department of Pharmaceutical Sciences, University of Antwerp, Universiteitsplein 1, 2610 Antwerp, Belgium

² Laboratory of Parasitology, Microbiology and Hygiene (LMPH), Faculty of Pharmaceutical, Biomedical and Veterinary Sciences, University of Antwerp, Universiteitsplein 1, 2610 Antwerp, Belgium

Molecules 2016, 21(10), 1287; https://doi.org/10.3390/molecules21101287 - 26 Sep 2016

Cited by 33 | Viewed by 6244

Abstract

The exudate of Ferula narthex Boiss. (Apiaceae) is widely used in the Indian subcontinent as a spice and because of its health effects. Six sesquiterpene coumarins have been isolated from this exudate: feselol, ligupersin A, asacoumarin A, 8′-O-acetyl-asacoumarin A, 10′R [...] Read more.

The exudate of Ferula narthex Boiss. (Apiaceae) is widely used in the Indian subcontinent as a spice and because of its health effects. Six sesquiterpene coumarins have been isolated from this exudate: feselol, ligupersin A, asacoumarin A, 8′-O-acetyl-asacoumarin A, 10′R-karatavacinol and 10′R-acetyl-karatavacinol. Based on its use in infectious and diabetic conditions, the isolated constituents were evaluated for antimicrobial and antiglycation activities. Some compounds showed activity against protozoal parasites, asacoumarin A being the most active one against Plasmodium falciparum K1 (IC₅₀ 1.3 μM). With regard to antiglycation activity, in the BSA-glucose test, ligupersin A displayed the highest activity (IC₅₀ 0.41 mM), being more active than the positive control aminiguanidine (IC₅₀ 1.75 mM). In the BSA-MGO assay, the highest activity was shown by 8′-O-acetyl-asacoumarin A (IC₅₀ 1.03 mM), being less active than aminoguanidine (IC₅₀ 0.15 mM). Hence, the antiglycation activity of the isolated constituents was due to both oxidative and non-oxidative modes of inhibition. Full article

(This article belongs to the Collection Natural Products as Leads or Drugs against Neglected Tropical Diseases)

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60 pages, 12699 KiB

Open AccessReview

Advances in Organic and Organic-Inorganic Hybrid Polymeric Supports for Catalytic Applications

by Anna Maria Pia Salvo, Francesco Giacalone

and Michelangelo Gruttadauria^*

Dipartimento Scienze e Tecnologie Biologiche, Chimiche e Farmaceutiche (STEBICEF) Università di Palermo, Viale delle Scienze, Ed. 17, 90128 Palermo, Italy

Molecules 2016, 21(10), 1288; https://doi.org/10.3390/molecules21101288 - 28 Sep 2016

Cited by 43 | Viewed by 13157

Abstract

In this review, the most recent advances (2014–2016) on the synthesis of new polymer-supported catalysts are reported, focusing the attention on the synthetic strategies developed for their preparation. The polymer-supported catalysts examined will be organic-based polymers and organic-inorganic hybrids and will include, among [...] Read more.

In this review, the most recent advances (2014–2016) on the synthesis of new polymer-supported catalysts are reported, focusing the attention on the synthetic strategies developed for their preparation. The polymer-supported catalysts examined will be organic-based polymers and organic-inorganic hybrids and will include, among others, polystyrenes, poly-ionic liquids, chiral ionic polymers, dendrimers, carbon nanotubes, as well as silica and halloysite-based catalysts. Selected examples will show the synthesis and application in the field of organocatalysis and metal-based catalysis both for non-asymmetric and asymmetric transformations. Full article

(This article belongs to the Special Issue Recent Advancements in Polymer-Supported Catalysis)

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15 pages, 4255 KiB

Open AccessArticle

CO Oxidation over Pd/ZrO₂ Catalysts: Role of Support′s Donor Sites

by Aleksey A. Vedyagin^1,2,*

, Alexander M. Volodin¹, Roman M. Kenzhin¹, Vladimir V. Chesnokov¹ and Ilya V. Mishakov^1,3

¹ Boreskov Institute of Catalysis SB RAS, Novosibirsk 630090, Russian

² Institute of Natural Resources, National Research Tomsk Polytechnic University, Tomsk 634050, Russian

³ Institute of Power Engineering, National Research Tomsk Polytechnic University, Tomsk 634050, Russian

Molecules 2016, 21(10), 1289; https://doi.org/10.3390/molecules21101289 - 27 Sep 2016

Cited by 40 | Viewed by 7042

Abstract

A series of supported Pd/ZrO₂ catalysts with Pd loading from 0.2 to 2 wt % was synthesized. The ZrO₂ material prepared by a similar technique was used as a reference sample. The samples have been characterized by means of transmission electron [...] Read more.

A series of supported Pd/ZrO₂ catalysts with Pd loading from 0.2 to 2 wt % was synthesized. The ZrO₂ material prepared by a similar technique was used as a reference sample. The samples have been characterized by means of transmission electron microscopy (TEM), X-ray diffraction analysis (XRD), X-ray photoelectron spectroscopy (XPS), temperature-programmed reduction (TPR), testing reaction of ethane hydrogenolysis (HGE), N₂ adsorption, and electron paramagnetic resonance (EPR) spectroscopy. 1,3,5-trinitrobenzene was used as a probe molecule for the EPR spin probe method. The catalytic performance of samples was tested in the model reaction of CO oxidation. It was shown that the concentration of donor sites of support measured by EPR spin probe correlates with catalytic behavior during light-off tests. Low concentration of donor sites on a support’s surface was found to be caused by the presence of the specific surface defects that are related to existence of coordinately unsaturated structures. Full article

(This article belongs to the Special Issue Palladium Catalysts 2016)

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11 pages, 652 KiB

Open AccessArticle

Design, Synthesis, and Cytotoxicity of 5-Fluoro-2-methyl-6-(4-aryl-piperazin-1-yl) Benzoxazoles

by Thuraya Al-Harthy¹, Wajdi Michel Zoghaib¹, Maren Pflüger², Miriam Schöpel³, Kamil Önder⁴, Maria Reitsammer⁴, Harald Hundsberger², Raphael Stoll³ and Raid Abdel-Jalil^1,*

¹ Chemistry Department, College of Science, Sultan Qaboos University, Muscat 123, Oman

² IMC Fachhochschule Krems University of Applied Sciences Krems, Piaristengasse 1, Krems A-3500, Austria

³ Biomolecular NMR, Ruhr University of Bochum, Bochum 44780, Germany

⁴ Research Program for Rational Drug Design in Dermatology and Rheumatolog, Department of Dermatology, General Hospital of Salzburg, Paracelsus Medical, University of Salzburg, Müllner Hauptstraße 48, Salzburg A-5020, Austria

Molecules 2016, 21(10), 1290; https://doi.org/10.3390/molecules21101290 - 27 Sep 2016

Cited by 14 | Viewed by 6440

Abstract

To design new compounds suitable as starting points for anticancer drug development, we have synthesized a novel series of benzoxazoles with pharmaceutically advantageous piperazine and fluorine moieties attached to them. The newly synthesized benzoxazoles and their corresponding precursors were evaluated for cytotoxicity on [...] Read more.

To design new compounds suitable as starting points for anticancer drug development, we have synthesized a novel series of benzoxazoles with pharmaceutically advantageous piperazine and fluorine moieties attached to them. The newly synthesized benzoxazoles and their corresponding precursors were evaluated for cytotoxicity on human A-549 lung carcinoma cells and non-cancer HepaRG hepatocyes. Some of these new benzoxazoles show potential anticancer activity, while two of the intermediates show lung cancer selective properties at low concentrations where healthy cells are unaffected, indicating a selectivity window for anticancer compounds. Full article

(This article belongs to the Section Medicinal Chemistry)

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12 pages, 1929 KiB

Open AccessArticle

Glycyrrhizic Acid Reduces Heart Rate and Blood Pressure by a Dual Mechanism

by Kailash Singh¹, Aung Moe Zaw¹, Revathi Sekar¹, Ahuja Palak¹, Ahmed A. Allam^2,3, Jamaan Ajarem² and Billy K. C. Chow^1,*

¹ School of Biological Sciences, The University of Hong Kong, Pokfulam Road, Hong Kong SAR, China

² Department of Zoology, College of Science, King Saud University, Riyadh 11451, Saudi Arabia

³ Department of Zoology, Faculty of Science, Beni-Suef University, Beni-Suef 62511, Egypt

Molecules 2016, 21(10), 1291; https://doi.org/10.3390/molecules21101291 - 27 Sep 2016

Cited by 15 | Viewed by 6896

Abstract

Beta adrenergic receptors are crucial for their role in rhythmic contraction of heart along with their role in the pathological conditions such as tachycardia and high risk of heart failure. Studies report that the levels of beta-1 adrenergic receptor tend to decrease by [...] Read more.

Beta adrenergic receptors are crucial for their role in rhythmic contraction of heart along with their role in the pathological conditions such as tachycardia and high risk of heart failure. Studies report that the levels of beta-1 adrenergic receptor tend to decrease by 50%, whereas, the levels of beta-2 adrenergic receptor remains constant during the risk of heart failure. Beta blockers—the antagonistic molecules for beta-adrenergic receptors, function by slowing the heart rate, which thereby allows the left ventricle to fill completely during tachycardia incidents and hence helps in blood pumping capacity of heart and reducing the risk of heart failure. In the present study, we investigate the potential of glycyrrhizic acid (GA) as a possible principal drug molecule for cardiac arrhythmias owing to its ability to induce reduction in the heart rate and blood pressure. We use in vitro and in silico approach to study GA′s effect on beta adrenergic receptor along with an in vivo study to examine its effect on heart rate and blood pressure. Additionally, we explore GA′s proficiency in eliciting an increase in the plasma levels of vasoactive intestinal peptide, which by dilating the blood vessel consequently, can be a crucial aid during the occurrence of a potential heart attack. Therefore, we propose GA as a potential principal drug molecule via its potential in modulating heart rate and blood pressure. Full article

(This article belongs to the Special Issue Structure-Activity Relationship of Natural Products)

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13 pages, 1181 KiB

Open AccessArticle

Phytochemical Compositions of Immature Wheat Bran, and Its Antioxidant Capacity, Cell Growth Inhibition, and Apoptosis Induction through Tumor Suppressor Gene

by Mi Jeong Kim¹, Won-Jin Yoon² and Sang Sook Kim^1,*

¹ Division of Funcitonal Food Research, Korea Food Research Institute, 62, Anyangpangyo-ro 1201 beon-gil, Bundang-gu, Seongnam-si, Gyeonggi-do 13539, Korea

² Division of Strategic Food Research, Korea Food Research Institute, 62, Anyangpangyo-ro 1201 beon-gil, Bundang-gu, Seongnam-si, Gyeonggi-do 13539, Korea

Molecules 2016, 21(10), 1292; https://doi.org/10.3390/molecules21101292 - 27 Sep 2016

Cited by 21 | Viewed by 6225

Abstract

The purpose of this study was to investigate the phytochemical compositions and antioxidant capacity, cell growth inhibition, and apoptosis induction in extracts of immature wheat bran. Immature wheat bran (IWB) was obtained from immature wheat harvested 10 days earlier than mature wheat. The [...] Read more.

The purpose of this study was to investigate the phytochemical compositions and antioxidant capacity, cell growth inhibition, and apoptosis induction in extracts of immature wheat bran. Immature wheat bran (IWB) was obtained from immature wheat harvested 10 days earlier than mature wheat. The phytochemical compositions of bran extract samples were analyzed by ultra-high performance liquid chromatography. The total ferulic acid (3.09 mg/g) and p-coumaric acid (75 µg/g) in IWB were significantly higher than in mature wheat bran (MWB, ferulic acid: 1.79 mg/g; p-coumaric acid: 55 µg/g). The oxygen radical absorbance capacity (ORAC: 327 µM Trolox equivalents (TE)/g) and cellular antioxidant activity (CAA: 4.59 µM Quercetin equivalents (QE)/g) of the IWB were higher than those of the MWB (ORAC: 281 µM TE/g; CAA: 0.63 µM QE/g). When assessing cell proliferation, the IWB extracts resulted in the lowest EC₅₀ values against HT-29 (18.9 mg/mL), Caco-2 (7.74 mg/mL), and HeLa cells (8.17 mg/mL) among bran extract samples. Additionally, the IWB extracts increased the gene expression of p53 and PTEN (tumor suppressor genes) in HT-29 cells, indicating inhibited cell growth and induced apoptosis through tumor suppressor genes. Full article

(This article belongs to the Collection Bioactive Compounds)

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13 pages, 1918 KiB

Open AccessArticle

Group I Intron Internal Guide Sequence Binding Strength as a Component of Ribozyme Network Formation

by Laura Elizabeth Satterwhite, Jessica A. M. Yeates and Niles Lehman^*

Department of Chemistry, Portland State University, Portland, OR 97202, USA

Molecules 2016, 21(10), 1293; https://doi.org/10.3390/molecules21101293 - 27 Sep 2016

Cited by 5 | Viewed by 5742

Abstract

Origins-of-life research requires searching for a plausible transition from simple chemicals to larger macromolecules that can both hold information and catalyze their own production. We have previously shown that some group I intron ribozymes possess the ability to help synthesize other ribozyme genotypes [...] Read more.

Origins-of-life research requires searching for a plausible transition from simple chemicals to larger macromolecules that can both hold information and catalyze their own production. We have previously shown that some group I intron ribozymes possess the ability to help synthesize other ribozyme genotypes by recombination reactions in small networks in an autocatalytic fashion. By simplifying these recombination reactions, using fluorescent anisotropy, we quantified the thermodynamic binding strength between two nucleotides of two group I intron RNA fragments for all 16 possible genotype combinations. We provide evidence that the binding strength (K_D) between the 3-nucleotide internal guide sequence (IGS) of one ribozyme and its complement in another is correlated to the catalytic ability of the ribozyme. This work demonstrates that one can begin to deconstruct the thermodynamic basis of information in prebiotic RNA systems. Full article

(This article belongs to the Special Issue Ribozymes and RNA Catalysis)

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13 pages, 3128 KiB

Open AccessArticle

Enzymatic Synthesis of Glucose-Based Fatty Acid Esters in Bisolvent Systems Containing Ionic Liquids or Deep Eutectic Solvents

by Kai-Hua Zhao¹, Yu-Zheng Cai², Xiao-Sheng Lin¹, Jun Xiong², Peter J. Halling³ and Zhen Yang^1,*

¹ College of Life Sciences and Oceanography, Shenzhen Key Laboratory of Microbial Genetic Engineering, Shenzhen University, Shenzhen 518060, Guangdong, China

² College of Life Sciences and oceanography, Shenzhen Key Laboratory of Marine Bioresources and Ecology, Shenzhen University, Shenzhen 518060, Guangdong, China

³ WestCHEM, Department of Pure & Applied Chemistry, University of Strathclyde, Glasgow G1 1XL, UK

Molecules 2016, 21(10), 1294; https://doi.org/10.3390/molecules21101294 - 27 Sep 2016

Cited by 44 | Viewed by 11638

Abstract

Sugar fatty acid esters (SFAEs) are biocompatible nonionic surfactants with broad applications in food, cosmetic, and pharmaceutical industries. They can be synthesized enzymatically with many advantages over their chemical synthesis. In this study, SFAE synthesis was investigated by using two reactions: (1) transesterification [...] Read more.

Sugar fatty acid esters (SFAEs) are biocompatible nonionic surfactants with broad applications in food, cosmetic, and pharmaceutical industries. They can be synthesized enzymatically with many advantages over their chemical synthesis. In this study, SFAE synthesis was investigated by using two reactions: (1) transesterification of glucose with fatty acid vinyl esters and (2) esterification of methyl glucoside with fatty acids, catalyzed by Lipozyme TLIM and Novozym 435 respectively. Fourteen ionic liquids (ILs) and 14 deep eutectic solvents (DESs) were screened as solvents, and the bisolvent system composed of 1-hexyl-3-methylimidazolium trifluoromethylsulfonate ([HMIm][TfO]) and 2-methyl-2-butanol (2M2B) was the best for both reactions, yielding optimal productivities (769.6 and 397.5 µmol/h/g, respectively) which are superior to those reported in the literature. Impacts of different reaction conditions were studied for both reactions. Response surface methodology (RSM) was employed to optimize the transesterification reaction. Results also demonstrated that as co-substrate, methyl glucoside yielded higher conversions than glucose, and that conversions increased with an increase in the chain length of the fatty acid moieties. DESs were poor solvents for the above reactions presumably due to their high viscosity and high polarity. Full article

(This article belongs to the Special Issue Ionic Liquids and Deep Eutectic Solvents for Synthesis, Materials and Energy)

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15 pages, 1527 KiB

Open AccessArticle

Palladium-Catalyzed Allylation/Benzylation of H-Phosphinate Esters with Alcohols

by Anthony Fers-Lidou, Olivier Berger and Jean-Luc Montchamp^*

Department of Chemistry and Biochemistry, TCU Box 298860, Texas Christian University, Fort Worth, TX 76129, USA

Molecules 2016, 21(10), 1295; https://doi.org/10.3390/molecules21101295 - 28 Sep 2016

Cited by 13 | Viewed by 7998

Abstract

The Pd-catalyzed direct alkylation of H-phosphinic acids and hypophosphorous acid with allylic/benzylic alcohols has been described previously. Here, the extension of this methodology to H-phosphinate esters is presented. The new reaction appears general, although its scope is narrower than with the [...] Read more.

The Pd-catalyzed direct alkylation of H-phosphinic acids and hypophosphorous acid with allylic/benzylic alcohols has been described previously. Here, the extension of this methodology to H-phosphinate esters is presented. The new reaction appears general, although its scope is narrower than with the acids, and its mechanism is likely different. Various alcohols are examined in their reaction with phosphinylidene compounds R¹R²P(O)H. Full article

(This article belongs to the Special Issue Recent Advances in Organophosphorus Chemistry)

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11 pages, 2088 KiB

Open AccessArticle

Constituents of Cryptotaenia japonica Inhibit Melanogenesis via CREB- and MAPK-Associated Signaling Pathways in Murine B16 Melanoma Cells

by Zuh-Kyung Seong^1,2

, Sung-Yoon Lee¹, Amrit Poudel¹, Sei-Ryang Oh^1,2 and Hyeong-Kyu Lee^1,2,*

¹ Natural Medicine Research Center, Korea Research Institute of Bioscience & Biotechnology, Yeongudanji-ro 30, Ochang-eup, Cheongwon-gu, Cheongju-si 28116, Korea

² Biomolecular Science, University of Science & Technology, 217 Gajeong-roYuseong-gu, Daejeon 34113, Korea

Molecules 2016, 21(10), 1296; https://doi.org/10.3390/molecules21101296 - 28 Sep 2016

Cited by 14 | Viewed by 6077

Abstract

Melanin plays an important role in protecting the skin against ultraviolet light and is responsible for skin color. However, overproduction of melanin is related to several skin disorders, such as age spots, freckles, café au lait spots, Becker’s nevus and other hyperpigmentation syndromes. [...] Read more.

Melanin plays an important role in protecting the skin against ultraviolet light and is responsible for skin color. However, overproduction of melanin is related to several skin disorders, such as age spots, freckles, café au lait spots, Becker’s nevus and other hyperpigmentation syndromes. The aim of this study was to identify the effects of kaempferol-7-O-β-d-glucuronide (K7G) and tilianin, isolated from Cryptotaenia japonica, on melanogenesis and their mechanisms of action in murine B16 melanoma cells. The α-melanocyte-stimulating hormone (α-MSH)-induced melanin production was significantly inhibited by K7G and tilianin in a dose-dependent manner. The effects of these compounds on the signaling pathway of melanogenesis were examined. K7G and tilianin downregulated the expression of microphthalmia-associated transcription factor (MITF) and melanocyte-specific enzymes, i.e., tyrosinase and TRP1. These compounds also inhibited the phosphorylation of cyclic adenosine monophosphate (cAMP)-response element binding protein (CREB) in a dose-dependent manner. In addition, these compounds increased the phosphorylation of extracellular signal-regulated kinase (ERK) but decreased the phosphorylation of c-Jun N-terminal kinase (JNK) in B16 cells. Based on the above results, the anti-melanogenic effects of these compounds are caused by suppression of the MAPK signaling pathway through the down-regulation of α-MSH-induced CREB accumulation. This finding suggests that K7G and tilianin may be good candidates for further research to develop therapeutic agents for hyperpigmentation diseases. Full article

(This article belongs to the Section Natural Products Chemistry)

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28 pages, 9305 KiB

Open AccessArticle

Mining Chromatographic Enantioseparation Data Using Matched Molecular Pair Analysis

by Robert P. Sheridan^1,*, Patrick Piras^2,*, Edward C. Sherer¹, Christian Roussel², William H. Pirkle³ and Christopher J. Welch^4,*

¹ Department of Structural Chemistry, Merck Research Laboratories, Rahway, NJ 07065, USA

² Aix Marseille Université, Centrale Marseille, CNRS, iSm2, 13397 Marseille CEDEX 20, France

³ Department of Chemistry, University of Illinois, Urbana, IL 61801, USA

⁴ Department of Process Research & Development, Merck Research Laboratories, Rahway, NJ 07055, USA

Molecules 2016, 21(10), 1297; https://doi.org/10.3390/molecules21101297 - 29 Sep 2016

Cited by 7 | Viewed by 6771

Abstract

We apply matched molecular pair (MMP) analysis to data from ChirBase, which contains literature reports of chromatographic enantioseparations. For the 19 chiral stationary phases we examined, we were able to identify 289 sets of pairs where there is a statistically significant and consistent [...] Read more.

We apply matched molecular pair (MMP) analysis to data from ChirBase, which contains literature reports of chromatographic enantioseparations. For the 19 chiral stationary phases we examined, we were able to identify 289 sets of pairs where there is a statistically significant and consistent difference in enantioseparation due to a small chemical change. In many cases these changes highlight enantioselectivity differences between pairs or small families of closely related molecules that have for many years been used to probe the mechanisms of chromatographic chiral recognition; for example, the comparison of N-H vs. N-Me analytes to determine the criticality of an N-H hydrogen bond in chiral molecular recognition. In other cases, statistically significant MMPs surfaced by the analysis are less familiar or somewhat puzzling, sparking a need to generate and test hypotheses to more fully understand. Consequently, mining of appropriate datasets using MMP analysis provides an important new approach for studying and understanding the process of chromatographic enantioseparation. Full article

(This article belongs to the Special Issue Chromatographic Separation of Enantiomers: Commemorative Issue in Honor of Professor Stig Allenmark on the Occasion of His 80th Birthday)

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7 pages, 744 KiB

Open AccessArticle

Identification of the Main Intermediate Precursor of l-Ergothioneine Biosynthesis in Human Biological Specimens

by Salvatore Sotgia^1,*

, Arduino A. Mangoni²

, Mauro Forteschi¹, Rhys B. Murphy²

, David Elliot², Elisabetta Sotgiu¹, Gianfranco Pintus^1,3

, Ciriaco Carru^1,4

and Angelo Zinellu¹

¹ Department of Biomedical Sciences, School of Medicine, University of Sassari, Sassari 07100, Italy

² Department of Clinical Pharmacology, School of Medicine, Flinders University and Flinders Medical Centre, Adelaide SA 5042, Australia

³ Department of Biomedical Sciences, College of Health Sciences, Qatar University, Doha 2713, Qatar

⁴ Quality Control Unit, University Hospital Sassari (AOU), Sassari 07100, Italy

Molecules 2016, 21(10), 1298; https://doi.org/10.3390/molecules21101298 - 28 Sep 2016

Cited by 13 | Viewed by 6508

Abstract

A capillary electrophoresis coupled to tandem mass spectrometry (CE–MS/MS) has been used to make a qualitative determination of hercynine—the main precursor of l-ergothioneine biosynthesis—in some key human biological specimens, such as urine, whole blood, plasma, and saliva. From semiquantitative analysis results, the [...] Read more.

A capillary electrophoresis coupled to tandem mass spectrometry (CE–MS/MS) has been used to make a qualitative determination of hercynine—the main precursor of l-ergothioneine biosynthesis—in some key human biological specimens, such as urine, whole blood, plasma, and saliva. From semiquantitative analysis results, the highest concentrations of hercynine were detected in saliva and whole blood, whereas much lower concentrations were measured in urine and plasma. Whole blood was the biological matrix with the highest concentration of l-ergothioneine followed by plasma, saliva, and urine. The antioxidant effects attributed to l-ergothioneine, along with its peculiar antioxidant mechanism, offer a possible explanation for the presence of the hercynine, as well as its concentration, in the considered biological matrices. Full article

(This article belongs to the Section Metabolites)

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9 pages, 1334 KiB

Open AccessArticle

New Diphenol and Isocoumarins from the Aerial Part of Lawsonia inermis and Their Inhibitory Activities against NO Production

by Chang-Syun Yang^1,†

, Hui-Chi Huang¹

, Sheng-Yang Wang^2,3,4, Ping-Jyun Sung^5,6

, Guan-Jhong Huang^1,†, Jih-Jung Chen^7,8,†

and Yueh-Hsiung Kuo^1,9,*

¹ Department of Chinese Pharmaceutical Sciences and Chinese Medicine Resources, China Medical University, Taichung 404, Taiwan

² Department of Forestry, National Chung-Hsing University, Taichung 402, Taiwan

³ Agricultural Biotechnology Research Center, Academia Sinica, Taipei 115, Taiwan

⁴ Agricultural Biotechnology Center, National Chung-Hsing University, Taichung 402, Taiwan

⁵ Graduate Institute of Marine Biotechnology and Department of Life Science and Institute of Biotechnology, National Dong Hwa University, Pingtung 944, Taiwan

⁶ National Museum of Marine Biology and Aquarium, Pingtung 944, Taiwan

⁷ Department of Pharmacy, Tajen University, Pingtung 907, Taiwan

⁸ Department of Medical Research, China Medical University Hospital, China Medical University, Taichung 404, Taiwan

⁹ Department of Biotechnology, Asia University, Taichung 413, Taiwan

Molecules 2016, 21(10), 1299; https://doi.org/10.3390/molecules21101299 - 28 Sep 2016

Cited by 17 | Viewed by 5363

Abstract

Lawsonia inermis Linn (Lythraceae), also known as henna, is a small shrub or tree distributed throughout Taiwan’s Lanyu Island, in North Africa, and in Australia. Its leaves are used as a folk medicine for the treatment of external hemorrhage and fingernail abscesses. Investigation [...] Read more.

Lawsonia inermis Linn (Lythraceae), also known as henna, is a small shrub or tree distributed throughout Taiwan’s Lanyu Island, in North Africa, and in Australia. Its leaves are used as a folk medicine for the treatment of external hemorrhage and fingernail abscesses. Investigation of the ethyl acetate (EtOAc)-soluble fractions from methanol extract of the aerial part of Lawsonia inermis has led to the isolation of a new diphenol, (Z)-4,4′-(prop-1-ene-1,3-diyl)diphenol (1), two new isocoumarin carbonates, inermiscarbonates A (2) and B (3), and six known compounds, 4′-hydroxyflavanone (4), apigenine (5), kampferol (6), luteolin (7), quercetin (8), and (-)-catechin (9). Their structures were determined by detailed analysis of spectroscopic data and comparison with the data of known analogues. Compounds 1 and 4–9 were evaluated for the inhibition of nitric oxide production in lipopolysaccharide (LPS)-stimulated product of nitrite in RAW 264.7 cells with IC₅₀ values of 5.63, 15.72, 8.67, 6.67, 6.17, 7.61, and 14.52 μg/mL, respectively. Full article

(This article belongs to the Collection Bioactive Compounds)

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16 pages, 2725 KiB

Open AccessArticle

Flavonoid Interaction with a Chitinase from Grape Berry Skin: Protein Identification and Modulation of the Enzymatic Activity

by Antonio Filippi¹, Elisa Petrussa¹

, Uros Rajcevic², Vladka Čurin Šerbec², Sabina Passamonti³, Giovanni Renzone⁴, Andrea Scaloni⁴, Marco Zancani¹, Angelo Vianello¹ and Enrico Braidot^1,*

¹ Department of Agricultural, Food, Animal and Environmental Sciences, University of Udine, Via delle Scienze 91, 33100 Udine, Italy

² Blood Transfusion Centre of Slovenia, Department of R&D, Šlajmerjeva 6, 1000 Ljubljana, Slovenia

³ Department of Life Sciences, University of Trieste, via L. Giorgieri 1, 34127 Trieste, Italy

⁴ Proteomics and Mass Spectrometry Laboratory, ISPAAM, CNR, via Argine, 1085-80147 Napoli, Italy

Molecules 2016, 21(10), 1300; https://doi.org/10.3390/molecules21101300 - 28 Sep 2016

Cited by 9 | Viewed by 5808

Abstract

In the present study, an antibody raised against a peptide sequence of rat bilitranslocase (anti-peptide Ab) was tested on microsomal proteins obtained from red grape berry skin. Previously, this antibody had demonstrated to recognize plant membrane proteins associated with flavonoid binding and transport. [...] Read more.

In the present study, an antibody raised against a peptide sequence of rat bilitranslocase (anti-peptide Ab) was tested on microsomal proteins obtained from red grape berry skin. Previously, this antibody had demonstrated to recognize plant membrane proteins associated with flavonoid binding and transport. Immuno-proteomic assays identified a number of proteins reacting with this particular antibody, suggesting that the flavonoid binding and interaction may be extended not only to carriers of these molecules, but also to enzymes with very different functions. One of these proteins is a pathogenesis-related (PR) class IV chitinase, whose in vitro chitinolytic activity was modulated by two of the most representative flavonoids of grape, quercetin and catechin, as assessed by both spectrophotometric and fluorimetric assays in grape microsomes and commercial enzyme preparations. The effect of these flavonoids on the catalysis and its kinetic parameters was also evaluated, evidencing that they determine a hormetic dose-dependent response. These results highlight the importance of flavonoids not only as antioxidants or antimicrobial effectors, but also as modulators of plant growth and stress response. Implications of the present suggestion are here discussed in the light of environment and pesticide-reduction concerns. Full article

(This article belongs to the Special Issue Flavonoids: From Structure to Health Issues)

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15 pages, 2795 KiB

Open AccessArticle

Catalytic Synthesis of a New Series of Alkyl Uronates and Evaluation of Their Physicochemical Properties

by Huiling Lu¹, Audrey Drelich¹, Mehdi Omri², Isabelle Pezron¹, Anne Wadouachi² and Gwladys Pourceau^2,*

¹ TIMR EA 4297 UTC/ESCOM, Sorbonne University, University of Technology of Compiègne, Rue Personne de Roberval, Compiègne CEDEX 60200, France

² LG2A, UMR CNRS 7378—Chemistry Institute of Picardy FR CNRS 3085, University of Picardy Jules Verne, 33 rue Saint Leu, Amiens CEDEX 80039, France

Molecules 2016, 21(10), 1301; https://doi.org/10.3390/molecules21101301 - 28 Sep 2016

Cited by 11 | Viewed by 6170

Abstract

Large quantities (>3 g) of a new series of alkyl uronates were synthesized in two steps from commercial methyl hexopyranosides. Firstly, several tens of grams of free methyl α-d-glucopyranoside were selectively and quantitatively oxidized into corresponding sodium uronate using 2,2,6,6-tetramethyl-1-piperidinyloxy free [...] Read more.

Large quantities (>3 g) of a new series of alkyl uronates were synthesized in two steps from commercial methyl hexopyranosides. Firstly, several tens of grams of free methyl α-d-glucopyranoside were selectively and quantitatively oxidized into corresponding sodium uronate using 2,2,6,6-tetramethyl-1-piperidinyloxy free radical (TEMPO)-catalyzed oxidation. Hydrophobic chains of different length were then introduced by acid-mediated esterification with fatty alcohols (ethyl to lauryl alcohol) leading to the desired alkyl glucuronates with moderate to good yields (49%–72%). The methodology was successfully applied to methyl α-d-mannopyranoside and methyl β-d-galactopyranoside. Physicochemical properties, such as critical micelle concentration (CMC), equilibrium surface tension at CMC (γ_cmc), solubility, and Krafft temperature were measured, and the effect of structural modifications on surface active properties and micelle formation was discussed. Full article

(This article belongs to the Special Issue Catalysis Applied to Biomass—Toward Sustainable Processes and Chemicals)

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13 pages, 602 KiB

Open AccessArticle

Traceability of Satsuma Mandarin (Citrus unshiu Marc.) Honey through Nectar/Honey-Sac/Honey Pathways of the Headspace, Volatiles, and Semi-Volatiles: Chemical Markers

by Igor Jerković^1,*

, Saša Prđun², Zvonimir Marijanović³, Marina Zekić¹

, Dragan Bubalo², Lidija Svečnjak² and Carlo I. G. Tuberoso⁴

¹ Department of Organic Chemistry, Faculty of Chemistry & Technology, University of Split, Ruđera Boškovića 35, HR-21000 Split, Croatia

² Department of Fisheries, Apiculture and Special Zoology, Faculty of Agriculture, University of Zagreb, Svetošimunska 25, HR-10000 Zagreb, Croatia

³ Department of Food Technology, Marko Marulić Polytechnic in Knin, Petra Krešimira IV 30, HR-22300 Knin, Croatia

⁴ Department of Life and Environmental Sciences, University of Cagliari, via Ospedale 72, IT-09124 Cagliari, Italy

Molecules 2016, 21(10), 1302; https://doi.org/10.3390/molecules21101302 - 29 Sep 2016

Cited by 18 | Viewed by 7201

Abstract

Headspace solid-phase microextraction (HS-SPME) and ultrasonic solvent extraction (USE), followed by GC-MS/FID, were applied for monitoring the nectar (NE)/honey-sac (HoS)/honey (HO) pathways of the headspace, volatiles, and semi-volatiles. The major NE (4 varieties of Citrus unshiu) headspace compounds were linalool, α-terpineol, 1 [...] Read more.

Headspace solid-phase microextraction (HS-SPME) and ultrasonic solvent extraction (USE), followed by GC-MS/FID, were applied for monitoring the nectar (NE)/honey-sac (HoS)/honey (HO) pathways of the headspace, volatiles, and semi-volatiles. The major NE (4 varieties of Citrus unshiu) headspace compounds were linalool, α-terpineol, 1H-indole, methyl anthranilate, and phenylacetonitrile. Corresponding extracts contained, among others, 1H-indole, methyl anthranilate, 1,3-dihydro-2H-indol-2-one and caffeine. The major HoS headspace compounds were linalool, α-terpineol, 1,8-cineole, 1H-indole, methyl anthranilate, and cis-jasmone. Characteristic compounds from HoS extract were caffeine, 1H-indole, 1,3-dihydro-2H-indol-2-one, methyl anthranilate, and phenylacetonitrile. However, HO headspace composition was significantly different in comparison to NE and HoS with respect to phenylacetaldehyde and linalool derivatives abundance that appeared as the consequence of the hive conditions and the bee enzyme activity. C. unshiu honey traceability is determined by chemical markers: phenylacetaldehyde, phenylacetonitrile, linalool and its derivatives, as well as 1H-indole, 1,3-dihydro-2H-indol-2-one, and caffeine. Full article

(This article belongs to the Section Natural Products Chemistry)

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8 pages, 1512 KiB

Open AccessArticle

Increasing the Level of IRS-1 and Insulin Pathway Sensitivity by Natural Product Carainterol A

by Kaiqing Ma¹, Yanhong Miao^1,2, Yao Gao¹, Junsheng Tian¹, Li Gao¹, Deyong Ye^3,* and Xuemei Qin^1,*

¹ Modern Research Center for Traditional Chinese Medicine, Shanxi University, Taiyuan 030006, China

² College of Chemistry and Chemical Engineering, Shanxi University, Taiyuan 030006, China

³ Department of Medicinal Chemistry, School of Pharmacy, Fudan University, Shanghai 201203, China

Molecules 2016, 21(10), 1303; https://doi.org/10.3390/molecules21101303 - 29 Sep 2016

Cited by 4 | Viewed by 4873

Abstract

Carainterol A is a eudesmane sesquiterpenoid extracted from Caragana intermedia. We have reported that carainterol A showed potent glucose consumption activity in C₂C₁₂ muscle cells and the db/db mouse model. However, the mechanism of the hypoglycemic effect of carainterol [...] Read more.

Carainterol A is a eudesmane sesquiterpenoid extracted from Caragana intermedia. We have reported that carainterol A showed potent glucose consumption activity in C₂C₁₂ muscle cells and the db/db mouse model. However, the mechanism of the hypoglycemic effect of carainterol A remains elusive. In this article, we present a network pharmacology approach to predict the target and signaling pathway of carainterol A which was subsequently validated in HepG2 cells. It was demonstrated that carainterol A could increase the protein levels of IRS-1 and the downstream protein kinase AKT phosphorylation at a low micromolar level. These findings suggest that carainterol A can be a valuable lead compound and a promising chemical probe for the insulin signaling pathway. Full article

(This article belongs to the Section Natural Products Chemistry)

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11 pages, 1033 KiB

Open AccessCommunication

Nucleophilic Substitution on 2-Monosubstituted Quinoxalines Giving 2,3-Disubstituted Quinoxalines: Investigating the Effect of the 2-Substituent

by Ndumiso Thamsanqa Ndlovu

and Winston Nxumalo^*

Department of Chemistry, Faculty of Science and Agriculture, University of Limpopo, Private Bag X 1106, Sovenga 0727, South Africa

Molecules 2016, 21(10), 1304; https://doi.org/10.3390/molecules21101304 - 30 Sep 2016

Cited by 8 | Viewed by 6957

Abstract

An investigation on the effect of substituent at the 2-position of mono-substituted quinoxalines in the synthesis of di-substituted quinoxaline derivatives via nucleophilic substitution reactions, is reported. Di-substituted quinoxalines bearing aryl-alky, aryl-aryl, aryl-heteroaryl, aryl-alkynyl, and amino-alkyl substituents were prepared in moderate to good yields. [...] Read more.

An investigation on the effect of substituent at the 2-position of mono-substituted quinoxalines in the synthesis of di-substituted quinoxaline derivatives via nucleophilic substitution reactions, is reported. Di-substituted quinoxalines bearing aryl-alky, aryl-aryl, aryl-heteroaryl, aryl-alkynyl, and amino-alkyl substituents were prepared in moderate to good yields. 2-Monosubstituted quinoxalines bearing a phenyl and butyl substituent reacted readily with alkyl-, aryl-, heteroaryl- and alkynyl- nucluephiles, giving di-substituted quinoxalines. 2-Monosubstituted quinoxalines bearing an amine and alkynyl substituent only reacted with alkyl nucleophiles. Oxidative rearomatization to give 2,3-disubstituted quinoxaline products occurred in atmospheric O₂. Full article

(This article belongs to the Collection Heterocyclic Compounds)

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13 pages, 743 KiB

Open AccessReview

Beneficial Effects of Tea and the Green Tea Catechin Epigallocatechin-3-gallate on Obesity

by Takuji Suzuki¹, Monira Pervin², Shingo Goto^3,†, Mamoru Isemura^2,* and Yoriyuki Nakamura²

¹ Faculty of Education, Art and Science, Yamagata University, Yamagata 990-8560, Japan

² Tea Science Center, University of Shizuoka, Shizuoka 422-8526, Japan

³ Graduate School of Nutritional and Environmental Sciences, University of Shizuoka, Shizuoka 422-8526, Japan

Molecules 2016, 21(10), 1305; https://doi.org/10.3390/molecules21101305 - 29 Sep 2016

Cited by 169 | Viewed by 26332

Abstract

Green tea has been shown to have beneficial effects against cancer, obesity, atherosclerosis, diabetes, bacterial and viral infections, and dental caries. The catechin (−)-epigallocatechin-3-gallate (EGCG) has shown the highest biological activity among green tea catechins (GTCs) in most of the studies. While several [...] Read more.

Green tea has been shown to have beneficial effects against cancer, obesity, atherosclerosis, diabetes, bacterial and viral infections, and dental caries. The catechin (−)-epigallocatechin-3-gallate (EGCG) has shown the highest biological activity among green tea catechins (GTCs) in most of the studies. While several epidemiological studies have shown the beneficial effects of tea and GTCs on obesity, some studies have failed to do this. In addition, a large number of interventional clinical studies have shown these favorable effects, and cellular and animal experiments have supported those findings, and revealed the underlying anti-obesity mechanisms. One of the mechanisms is enhanced cellular production of reactive oxygen species, which is mediated through the pro-oxidant action of EGCG, leading to the activation of adenosine monophosphate-activated protein kinase, which suppresses gene and protein expression of enzymes and transcription factors involved in adipogenesis and lipogenesis, and stimulates those involved in lipolysis. Recently, scientific evidence supporting the beneficial anti-obesity effects of green tea and GTCs has been increasing. However, future investigations are still required to clarify the reasons for the inconsistent results reported in the human studies; to achieve this, careful adjustment of confounding factors will be required. Full article

(This article belongs to the Special Issue Natural Products in Anti-Obesity Therapy)

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12 pages, 1736 KiB

Open AccessArticle

Antidermatophytic Action of Resorcinol Derivatives: Ultrastructural Evidence of the Activity of Phenylethyl Resorcinol against Microsporum gypseum

by Carlo Romagnoli¹, Anna Baldisserotto²

, Chiara B. Vicentini², Donatella Mares², Elisa Andreotti¹, Silvia Vertuani² and Stefano Manfredini^2,*

¹ Department of Life Sciences, University of Modena and Reggio Emilia, Viale Caduti in Guerra 127, 41121 Modena, Italy

² Department of Life Sciences and Biotechnology, Master Course in Cosmetic Science and Technology, University of Ferrara, Via Fossato di Mortara 17-19, 44121 Ferrara, Italy

Molecules 2016, 21(10), 1306; https://doi.org/10.3390/molecules21101306 - 30 Sep 2016

Cited by 23 | Viewed by 6923

Abstract

In this work, we evaluated the antidermatophytic activities of three resorcinol derivatives that have a history of use in dermo-cosmetic applications to discover molecules with multiple dermatological activities (i.e., multi-target drugs), thereby reducing the cost and time necessary for new drug development. The [...] Read more.

In this work, we evaluated the antidermatophytic activities of three resorcinol derivatives that have a history of use in dermo-cosmetic applications to discover molecules with multiple dermatological activities (i.e., multi-target drugs), thereby reducing the cost and time necessary for new drug development. The antidermatophytic activities of the three skin lighteners were evaluated relative to the known antifungal drug fluconazole on nine dermatophytes responsible for the most common dermatomycoses: Microsporum gypseum, Microsporum canis, Trichophyton violaceum, Arthroderma cajetani, Trichophyton mentagrophytes, Epidermophyton floccosum, Nannizzia gypsea, Trichophyton rubrum and Trichophyton tonsurans. Among the three tested resorcinols, only two showed promising properties, with the ability to inhibit the growth of all tested dermatophytes; additionally, the IC₅₀ values of these two resorcinols against the nine dermatophytes confirmed their good antifungal activity, particularly for phenylethyl resorcinol against M. gypseum. Ultrastructural alterations exhibited by the fungus were observed using scanning electron microscopy and transmission electron microscopy and reflected a dose-dependent response to treatment with the activation of defence and self-preservation strategies. Full article

(This article belongs to the Section Medicinal Chemistry)

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19 pages, 2750 KiB

Open AccessArticle

Quantitative and Qualitative Analysis of Flavonoids and Phenolic Acids in Snow Chrysanthemum (Coreopsis tinctoria Nutt.) by HPLC-DAD and UPLC-ESI-QTOF-MS

by Yinjun Yang^1,2, Xinguang Sun², Jinjun Liu¹, Liping Kang², Sibao Chen¹, Baiping Ma² and Baolin Guo^1,*

¹ Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100193, China

² Department of Biology, Beijing Institute of Radiation Medicine, Beijing 100850, China

Molecules 2016, 21(10), 1307; https://doi.org/10.3390/molecules21101307 - 30 Sep 2016

Cited by 74 | Viewed by 8762

Abstract

A simple, accurate and reliable high performance liquid chromatography coupled with photodiode array detection (HPLC-DAD) method was developed and then successfully applied for simultaneous quantitative analysis of eight compounds, including chlorogenic acid (1), (R/S)-flavanomarein (2), [...] Read more.

A simple, accurate and reliable high performance liquid chromatography coupled with photodiode array detection (HPLC-DAD) method was developed and then successfully applied for simultaneous quantitative analysis of eight compounds, including chlorogenic acid (1), (R/S)-flavanomarein (2), butin-7-O-β-d-glucopyranoside (3), isookanin (4), taxifolin (5), 5,7,3′,5′-tetrahydroxyflavanone-7-O-β-d-glucopyranoside (6), marein (7) and okanin (8), in 23 batches of snow chrysanthemum of different seed provenance and from various habitats. The results showed total contents of the eight compounds in the samples with seed provenance from Keliyang (Xinjiang, China), are higher than in samples from the other five provenances by 52.47%, 15.53%, 19.78%, 21.17% and 5.06%, respectively, which demonstrated that provenance has a great influence on the constituents in snow chrysanthemum. Meanwhile, an ultra performance liquid chromatography coupled with electrospray ionization and quadrupole time-of-flight-mass spectrometry (UPLC-ESI-QTOF-MS) was also employed to rapidly separate and identify flavonoids and phenolic acids in snow chrysanthemum from Keliyang. As a result, a total of 30 constituents, including 26 flavonoids and four phenolic acids, were identified or tentatively identified based on the exact mass information, the fragmentation characteristics, and retention times of eight reference standards. This work may provide an efficient approach to comprehensively evaluate the quality of snow chrysanthemum. Full article

(This article belongs to the Section Natural Products Chemistry)

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9 pages, 10698 KiB

Open AccessArticle

Re-188 Enhances the Inhibitory Effect of Bevacizumab in Non-Small-Cell Lung Cancer

by Jie Xiao^1,2,†, Xiaobo Xu^3,†, Xiao Li^1,2, Yanli Li^1,2, Guobing Liu^1,2, Hui Tan^1,2, Hua Shen⁴, Hongcheng Shi^1,2 and Dengfeng Cheng^1,2,*

¹ Department of Nuclear Medicine, Zhongshan Hospital, Fudan University, Shanghai 200032, China

² Shanghai Institute of Medical Imaging, Shanghai 200032, China

³ Departments of Respiratory Medicine, Zhongshan Hospital, Fudan University, Shanghai 200032, China

⁴ Institute of Applied Physics, Chinese Academy of Sciences, Shanghai 200032, China

^† These authors contributed equally to this work.

Molecules 2016, 21(10), 1308; https://doi.org/10.3390/molecules21101308 - 30 Sep 2016

Cited by 11 | Viewed by 6412

Abstract

The malignant behaviors of solid tumors such as growth, infiltration and metastasis are mainly nourished by tumor neovascularization. Thus, anti-angiogenic therapy is key to controlling tumor progression. Bevacizumab, a humanized anti-vascular endothelial growth factor (VEGF) antibody, plus chemotherapy or biological therapy can prolong [...] Read more.

The malignant behaviors of solid tumors such as growth, infiltration and metastasis are mainly nourished by tumor neovascularization. Thus, anti-angiogenic therapy is key to controlling tumor progression. Bevacizumab, a humanized anti-vascular endothelial growth factor (VEGF) antibody, plus chemotherapy or biological therapy can prolong survival for cancer patients, but treatment-related mortality is a concern. To improve inhibitory effect and decrease side-effects on non-small-cell lung cancer (NSCLC), we used Re-188, which is a β emitting radionuclide, directly labeled with bevacizumab for radioimmunotherapy in a human A549 tumor model. Cytotoxic assay data showed that, after ¹⁸⁸ReO₄⁻ or ¹⁸⁸Re-bevacizumab at different concentration for 4 and 24 h, a time- and radioactivity does-dependent reduction in cell viability occurred. Also, an apoptosis assay conformed great apoptosis in the ¹⁸⁸Re-bevacizumab group compared with controls and other treatment groups. In vivo, tumor volumes in the ¹⁸⁸Re-bevacizumab (11.1 MBq/mice) group were not reduced but growth was delayed compared with other groups. Thus, ¹⁸⁸Re-bevacizumab enhanced the therapeutic effect of bevacizumab, suggesting a potential therapeutic strategy for NSCLC treatment. Full article

(This article belongs to the Special Issue Molecular Imaging Probes)

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10 pages, 2144 KiB

Open AccessCommunication

Synthesis of a 1-Aryl-2,2-chlorosilyl(phospha)silene Coordinated by an N-Heterocyclic Carbene

by Andreas Wolfgang Kyri^1,2, Paresh Kumar Majhi¹, Takahiro Sasamori^1,*

, Tomohiro Agou¹

, Vitaly Nesterov^1,2, Jing-Dong Guo¹, Shigeru Nagase³, Norihiro Tokitoh^1,* and Rainer Streubel^2,*

¹ Institute for Chemical Research, Kyoto University, Gokasho, Uji, 611-0011 Kyoto, Japan

² Institut für Anorganische Chemie der Rheinischen Friedrich-Wilhelms-Universität Bonn, Gerhard-Domagk-Str. 1, 53121 Bonn, Germany

³ Fukui Institute for Fundamental Chemistry, Kyoto University, 606-8103 Kyoto, Japan

Molecules 2016, 21(10), 1309; https://doi.org/10.3390/molecules21101309 - 30 Sep 2016

Cited by 11 | Viewed by 6258

Abstract

Phosphasilenes, P=Si doubly bonded compounds, have received considerable attention due to their unique physical and chemical properties. We report on the synthesis and structure of a chlorophosphasilene coordinated by an N-heterocyclic carbene (NHC), which has the potential of functionalization at the Si–Cl [...] Read more.

Phosphasilenes, P=Si doubly bonded compounds, have received considerable attention due to their unique physical and chemical properties. We report on the synthesis and structure of a chlorophosphasilene coordinated by an N-heterocyclic carbene (NHC), which has the potential of functionalization at the Si–Cl moiety. Treatment of a silylphosphine, ArPH–SiCl₂R_Si (Ar = bulky aryl group, R_Si = Si(SiMe₃)₃) with two equivalents of Im-Me₄ (1,3,4,5-tetramethylimidazol-2-ylidene) afforded the corresponding NHC-coordinated phosphasilene, ArP=SiClR_Si(Im-Me₄) as a stable compound. Bonding properties of the P=Si bond coordinated to an NHC will be discussed on the basis of theoretical calculations. Full article

(This article belongs to the Special Issue Advances in Silicon Chemistry)

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12 pages, 1215 KiB

Open AccessArticle

Real-Time Detection of a Self-Replicating RNA Enzyme

by Charles Olea and Gerald F. Joyce^*

Department of Chemistry and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 N. Torrey Pines Road, La Jolla, CA 92037, USA

Molecules 2016, 21(10), 1310; https://doi.org/10.3390/molecules21101310 - 30 Sep 2016

Cited by 10 | Viewed by 7839

Abstract

A system was developed to detect the self-replication of an RNA enzyme in real time. The enzyme is an RNA ligase that undergoes exponential amplification at a constant temperature and can be made to operate in a ligand-dependent manner. The real-time system is [...] Read more.

A system was developed to detect the self-replication of an RNA enzyme in real time. The enzyme is an RNA ligase that undergoes exponential amplification at a constant temperature and can be made to operate in a ligand-dependent manner. The real-time system is based on a fluorimetric readout that directly couples the ligation event to an increase in florescence signal that can be monitored using standard instrumentation. The real-time system can also operate entirely with l-RNA, which is not susceptible to degradation by ribonucleases that are present in biological samples. The system is analogous to real-time PCR, but with the potential to detect small molecules, proteins, and other targets that can be recognized by a suitable aptamer. The ligand-dependent self-replication of RNA has potential applications in molecular diagnostics and biosensing that benefit from the rapid, precise, and real-time detection of various target molecules. Full article

(This article belongs to the Special Issue Ribozymes and RNA Catalysis)

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17 pages, 1628 KiB

Open AccessArticle

Chlorella sorokiniana Extract Improves Short-Term Memory in Rats

by Maria Grazia Morgese¹, Emanuela Mhillaj², Matteo Francavilla^3,4

, Maria Bove², Lucia Morgano¹, Paolo Tucci¹, Luigia Trabace^1,*,† and Stefania Schiavone^1,†

¹ Department of Clinical and Experimental Medicine, University of Foggia, Foggia 71121, Italy

² Department of Physiology and Pharmacology, “Sapienza” University of Rome, Rome 00185, Italy

³ STAR Agroenergy Research Group, University of Foggia, Via Gramsci, 89-91, Foggia 71121, Italy

⁴ Institute of Marine Science, National Research Council, via Pola 4, Lesina 71010, Italy

Molecules 2016, 21(10), 1311; https://doi.org/10.3390/molecules21101311 - 29 Sep 2016

Cited by 26 | Viewed by 7487

Abstract

Increasing evidence shows that eukaryotic microalgae and, in particular, the green microalga Chlorella, can be used as natural sources to obtain a whole variety of compounds, such as omega (ω)-3 and ω-6 polyunsatured fatty acids (PUFAs). Although either beneficial or toxic effects [...] Read more.

Increasing evidence shows that eukaryotic microalgae and, in particular, the green microalga Chlorella, can be used as natural sources to obtain a whole variety of compounds, such as omega (ω)-3 and ω-6 polyunsatured fatty acids (PUFAs). Although either beneficial or toxic effects of Chlorella sorokiniana have been mainly attributed to its specific ω-3 and ω-6 PUFAs content, the underlying molecular pathways remain to be elucidated yet. Here, we investigate the effects of an acute oral administration of a lipid extract of Chlorella sorokiniana, containing mainly ω-3 and ω-6 PUFAs, on cognitive, emotional and social behaviour in rats, analysing possible underlying neurochemical alterations. Our results showed improved short-term memory in Chlorella sorokiniana-treated rats compared to controls, without any differences in exploratory performance, locomotor activity, anxiety profile and depressive-like behaviour. On the other hand, while the social behaviour of Chlorella sorokiniana-treated animals was significantly decreased, no effects on aggressivity were observed. Neurochemical investigations showed region-specific effects, consisting in an elevation of noradrenaline (NA) and serotonin (5-HT) content in hippocampus, but not in the prefrontal cortex and striatum. In conclusion, our results point towards a beneficial effect of Chlorella sorokiniana extract on short-term memory, but also highlight the need of caution in the use of this natural supplement due to its possible masked toxic effects. Full article

(This article belongs to the Special Issue Potential Neuromodulatory Profile of Phytocompounds in Brain Disorders)

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25 pages, 737 KiB

Open AccessReview

Neurodegenerative Diseases: Might Citrus Flavonoids Play a Protective Role?

by Santa Cirmi¹

, Nadia Ferlazzo¹, Giovanni E. Lombardo²

, Elvira Ventura-Spagnolo³, Sebastiano Gangemi^4,5, Gioacchino Calapai⁶ and Michele Navarra^1,*

¹ Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, viale Annunziata, Messina I-98168, Italy

² Department of Health Sciences, University “Magna Graecia” of Catanzaro, Catanzaro I-88100, Italy

³ Department of Biotechnology and Legal Medicine, University of Palermo, Palermo I-90127, Italy

⁴ Department of Clinical and Experimental Medicine, University of Messina, Messina I-98125, Italy

⁵ Institute of Applied Sciences and Intelligent Systems (ISASI), National Research Council (CNR), Pozzuoli I-80078, Italy

⁶ Department of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina, Messina I-98125, Italy

Molecules 2016, 21(10), 1312; https://doi.org/10.3390/molecules21101312 - 30 Sep 2016

Cited by 112 | Viewed by 12428

Abstract

Neurodegenerative diseases (ND) result from the gradual and progressive degeneration of the structure and function of the central nervous system or the peripheral nervous system or both. They are characterized by deterioration of neurons and/or myelin sheath, disruption of sensory information transmission and [...] Read more.

Neurodegenerative diseases (ND) result from the gradual and progressive degeneration of the structure and function of the central nervous system or the peripheral nervous system or both. They are characterized by deterioration of neurons and/or myelin sheath, disruption of sensory information transmission and loss of movement control. There is no effective treatment for ND, and the drugs currently marketed are symptom-oriented, albeit with several side effects. Within the past decades, several natural remedies have gained attention as potential neuroprotective drugs. Moreover, an increasing number of studies have suggested that dietary intake of vegetables and fruits can prevent or delay the onset of ND. These properties are mainly due to the presence of polyphenols, an important group of phytochemicals that are abundantly present in fruits, vegetables, cereals and beverages. The main class of polyphenols is flavonoids, abundant in Citrus fruits. Our review is an overview on the scientific literature concerning the neuroprotective effects of the Citrus flavonoids in the prevention or treatment of ND. This review may be used as scientific basis for the development of nutraceuticals, food supplements or complementary and alternative drugs to maintain and improve the neurophysiological status. Full article

(This article belongs to the Special Issue Potential Neuromodulatory Profile of Phytocompounds in Brain Disorders)

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8 pages, 495 KiB

Open AccessArticle

2-(2-Phenylethyl)chromone Derivatives of Agarwood Originating from Gyrinops salicifolia

by Hang Shao^1,2, Wen-Li Mei², Wen-Hua Dong², Cui-Juan Gai², Wei Li², Guo-Peng Zhu^1,*

and Hao-Fu Dai^2,*

¹ Horticultural and Garden College, Hainan University, Haikou 570228, Hainan, China

² Key Laboratory of Biology and Genetic Resources of Tropical Crops, Ministry of Agriculture, Institute of Tropical Bioscience and Biotechnology, Chinese Academy of Tropical Agricultural Sciences, Haikou 571101, Hainan, China

Molecules 2016, 21(10), 1313; https://doi.org/10.3390/molecules21101313 - 3 Oct 2016

Cited by 21 | Viewed by 5127

Abstract

Three new2-(2-phenylethyl)chromone derivatives (1–3) and a new2-(2-phenylethenyl)chromone derivative (4), together with two known 2-(2-phenylethyl)chromone derivatives (5–6), were isolated from agarwood originating from Gyrinops salicifolia Ridl. The structures of compounds 1–4 were elucidated by comprehensive spectroscopic techniques (UV, IR, 1D and 2D-NMR) and MS [...] Read more.

Three new2-(2-phenylethyl)chromone derivatives (1–3) and a new2-(2-phenylethenyl)chromone derivative (4), together with two known 2-(2-phenylethyl)chromone derivatives (5–6), were isolated from agarwood originating from Gyrinops salicifolia Ridl. The structures of compounds 1–4 were elucidated by comprehensive spectroscopic techniques (UV, IR, 1D and 2D-NMR) and MS analysis, as well as by comparison with the literature. Compounds 1, 2, and 5 showed moderate cytotoxicity against human tumor K562, BEL-7402, and SGC-7901 cell lines with IC50 values of 5.76 to 20.1 µM. Full article

(This article belongs to the Section Natural Products Chemistry)

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9 pages, 3450 KiB

Open AccessArticle

Synthesis of Polymer-Lipid Nanoparticles by Microfluidic Focusing for siRNA Delivery

by Yujing Li^1,†

, Xueqin Huang^1,2,†

, Robert J. Lee^1,3

, Yuhang Qi¹, Kaikai Wang¹, Fei Hao¹, Yu Zhang¹, Jiahui Lu¹, Qingfan Meng¹, Shuai Li¹, Jing Xie^1,* and Lesheng Teng^1,*

¹ School of Life Sciences, Jilin University, Qianjin Street No. 2699, Changchun 130012, China

² Department of Chemistry and Pharmacy, Zhuhai College of Jilin University, Zhuhai 519041, China

³ Division of Pharmaceutics, College of Pharmacy, The Ohio State University, Columbus, OH 43210, USA

^† These authors contributed equally to this work.

Molecules 2016, 21(10), 1314; https://doi.org/10.3390/molecules21101314 - 17 Oct 2016

Cited by 25 | Viewed by 7419

Abstract

Polyethylenimine (PEI) as a cationic polymer is commonly used as a carrier for gene delivery. PEI-800 is less toxic than PEI-25K but it is also less efficient. A novel nanocarrier was developed by combining PEI-800 with a pH-sensitive lipid to form polymer-lipid hybrid [...] Read more.

Polyethylenimine (PEI) as a cationic polymer is commonly used as a carrier for gene delivery. PEI-800 is less toxic than PEI-25K but it is also less efficient. A novel nanocarrier was developed by combining PEI-800 with a pH-sensitive lipid to form polymer-lipid hybrid nanoparticles (P/LNPs). They were synthesized by microfluidic focusing (MF). Two microfluidic devices were used to synthesize P/LNPs loaded with VEGF siRNA. A series of P/LNPs with different particle sizes and distributions were obtained by altering the flow rate and geometry of microfluidic chips, and introducing sonication. Furthermore, the P/LNPs can be loaded with VEGF siRNA efficiently and were stable in serum for 12 h. Finally, P/LNPs produced by the microfluidic chip showed greater cellular uptake as well as down-regulation of VEGF protein level in both A549 and MCF-7 with reduced cellular toxicity. All in all, the P/LNPs produced by MF method were shown to be a safe and efficient carrier for VEGF siRNA, with potential application for siRNA therapeutics. Full article

(This article belongs to the Special Issue Nucleic Acid-based Drug)

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11 pages, 3054 KiB

Open AccessArticle

SimCP3—An Advanced Homologue of SimCP2 as a Solution-Processed Small Molecular Host Material for Blue Phosphorescence Organic Light-Emitting Diodes

by Yi-Ting Lee¹, Yung-Ting Chang², Cheng-Lung Wu², Jan Golder³, Chin-Ti Chen^2,3,* and Chao-Tsen Chen^1,*

¹ Department of Chemistry, National Taiwan University, Taipei 10617, Taiwan

² Institute of Chemistry, Academia Sinica, Taipei 11529, Taiwan

³ Department of Applied Chemistry, National Chiao Tung University, Hsinchu 30050, Taiwan

Molecules 2016, 21(10), 1315; https://doi.org/10.3390/molecules21101315 - 30 Sep 2016

Viewed by 7047

Abstract

We have overcome the synthetic difficulty of 9,9′,9′′,9′′′,9′′′′,9′′′′′-((phenylsilanetriyl)tris(benzene-5,3,1-triyl))hexakis(9H-carbazole) (SimCP3) an advanced homologue of previously known SimCP2 as a solution-processed, high triplet gap energy host material for a blue phosphorescence dopant. A series of organic light-emitting diodes based on blue phosphorescence dopant [...] Read more.

We have overcome the synthetic difficulty of 9,9′,9′′,9′′′,9′′′′,9′′′′′-((phenylsilanetriyl)tris(benzene-5,3,1-triyl))hexakis(9H-carbazole) (SimCP3) an advanced homologue of previously known SimCP2 as a solution-processed, high triplet gap energy host material for a blue phosphorescence dopant. A series of organic light-emitting diodes based on blue phosphorescence dopant iridium (III) bis(4,6-difluorophenylpyridinato)picolate, FIrpic, were fabricated and tested to demonstrate the validity of solution-processed SimCP3 in the device fabrication. Full article

(This article belongs to the Special Issue Organic Light Emitting Diodes)

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19 pages, 2837 KiB

Open AccessArticle

A Set of 20 New SSR Markers Developed and Evaluated in Mandevilla Lindl.

by Alev Oder¹, Robert Lannes¹ and Maria Angeles Viruel^2,*

¹ S.A.S. DHMINNOVATION 18, Avenue du Quercy—BP5, 82200 Malause, France

² Instituto de Hortofruticultura Subtropical y Mediterránea La Mayora (IHSM-UMA-CSIC), 29750 Algarrobo-Costa (Málaga), Spain

Molecules 2016, 21(10), 1316; https://doi.org/10.3390/molecules21101316 - 30 Sep 2016

Cited by 7 | Viewed by 5553

Abstract

Mandevilla is an ornamental crop with a bright future worldwide because of its high commercial acceptance and added value. However, as with most ornamental species, there are few molecular tools to support cultivar breeding and innovation. In this work, we report the development [...] Read more.

Mandevilla is an ornamental crop with a bright future worldwide because of its high commercial acceptance and added value. However, as with most ornamental species, there are few molecular tools to support cultivar breeding and innovation. In this work, we report the development and analysis of 20 new Simple Sequence Repeat (SSR) markers in Mandevilla. Microsatellites were isolated from two enriched small-insert genomic libraries of Mandevilla × amabilis. The diversity parameters estimated after their amplification in a group of 11 commercial genotypes illustrate the effect of two opposite drifts: the high relatedness of cultivars belonging to the same commercial group and the high divergence of other cultivars, especially M. × amabilis. Based on their different band patterns, six genotypes were uniquely distinguished, and two groups of sport mutations remained undistinguishable. The amplification of the SSRs in three wild species suggested the existence of unexploited diversity available to be introgressed into the commercial pool. This is the first report of available microsatellites in Mandevilla. The development process has provided some clues concerning the genome structure of the species, and the SSRs obtained will help to create new products and to protect existing and upcoming plant innovations. Full article

(This article belongs to the Section Molecular Diversity)

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14 pages, 3423 KiB

Open AccessArticle

A Potential Mechanism for the Anti-Apoptotic Property of Koumine Involving Mitochondrial Pathway in LPS-Mediated RAW 264.7 Macrophages

by Zhi-Hang Yuan^1,2, Zeng-Enni Liang³, Jing Wu^1,2, Jin-E Yi^1,2, Xiao-Jun Chen^1,2 and Zhi-Liang Sun^1,2,*

¹ Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Hunan Agricultural University, Changsha 410128, China

² Hunan Co-Innovation Center for Utilization of Botanical Functional Ingredients, Changsha 410128, China

³ Department of Hunan Agricultural Product Processing Institute, Changsha 410128, China

Molecules 2016, 21(10), 1317; https://doi.org/10.3390/molecules21101317 - 1 Oct 2016

Cited by 26 | Viewed by 6991

Abstract

Koumine is a kind of alkaloid extracted from Gelsemium elegans (G. elegans). Benth, which has shown promise as an anti-tumor, anxiolytic, and analgesic agent. In our present study, the effect of koumine on lipopolysaccharide (LPS)-mediated RAW 264.7 cell apoptosis was evaluated. [...] Read more.

Koumine is a kind of alkaloid extracted from Gelsemium elegans (G. elegans). Benth, which has shown promise as an anti-tumor, anxiolytic, and analgesic agent. In our present study, the effect of koumine on lipopolysaccharide (LPS)-mediated RAW 264.7 cell apoptosis was evaluated. MTT assays showed that koumine obviously increased cell viability in LPS-mediated RAW 264.7 macrophages. Preincubation with koumine ameliorated LPS-medicated apoptosis by decreasing reactive oxygen species (ROS) production, which resulted in a significant decrease in the levels of nitric oxide (NO) and inducible nitric oxide synthase (iNOS). In addition, koumine-pretreated RAW 264.7 macrophages exhibited reduction of LPS-induced levels of TNF-α, IL-1β, and IL-6 mRNA. Furthermore, pretreatment with koumine suppressed LPS-mediated p53 activation, loss of mitochondrial membrane potential, caspase-3 activation, decrease of Bcl-2 expression, and elevation of Bax and caspase-3 expressions, suggesting that koumine might act directly on RAW 264.7 cells to inhibit LPS-induced apoptosis. It seems as though the mechanism that koumine possesses is the anti-apoptotic effect mediated by suppressing production of ROS, activation of p53, and mitochondrial apoptotic pathways in RAW 264 cells. Koumine could potentially serve as a protective effect against LPS-induced apoptosis. Full article

(This article belongs to the Special Issue Natural Products and Inflammation)

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10 pages, 3346 KiB

Open AccessArticle

Growing and Etching MoS₂ on Carbon Nanotube Film for Enhanced Electrochemical Performance

by Weiyu Xu^†, Qi Fang^†, Daobin Liu, Ke Zhang, Muhammad Habib, Chuanqiang Wu, Xusheng Zheng, Hengjie Liu

, Shuangming Chen and Li Song^*

¹ National Synchrotron Radiation Laboratory, CAS Center for Excellence in Nanoscience, University of Science and Technology of China, Hefei 230029, China

^† These authors contributed equally to this paper.

Molecules 2016, 21(10), 1318; https://doi.org/10.3390/molecules21101318 - 30 Sep 2016

Cited by 10 | Viewed by 7409

Abstract

In this work we directly synthesized molybdenum disulfide (MoS₂) nanosheets on carbon nanotube film (MoS₂@CNT) via a two-step chemical vapor deposition method (CVD). By etching the obtained MoS₂@CNT into 10% wt HNO₃, the morphology of [...] Read more.

In this work we directly synthesized molybdenum disulfide (MoS₂) nanosheets on carbon nanotube film (MoS₂@CNT) via a two-step chemical vapor deposition method (CVD). By etching the obtained MoS₂@CNT into 10% wt HNO₃, the morphology of MoS₂ decorated on CNT bundles was modulated, resulting in more catalytic active MoS₂ edges being exposed for significantly enhanced electrochemical performance. Our results revealed that an 8 h acid etching sample exhibited the best performance for the oxygen evolution reaction, i.e., the current density reached 10 mA/cm² under 375 mV over-potential, and the tafel slope was as low as 94 mV/dec. The enhanced behavior was mainly originated from the more catalytic sites in MoS₂ induced by the acid etching treatment and the higher conductivity from the supporting CNT films. Our study provides a new route to produce two-dimensional layers on CNT films with tunable morphology, and thus may open a window for exploring its promising applications in the fields of catalytic-, electronic-, and electrochemical-related fields. Full article

(This article belongs to the Special Issue Carbon Nanotubes: Advances and Applications)

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15 pages, 2641 KiB

Open AccessArticle

Molecular Electron Density Theory: A Modern View of Reactivity in Organic Chemistry

by Luis R. Domingo

Department of Organic Chemistry, University of Valencia, Dr. Moliner 50, Burjassot, Valencia E-46100, Spain

Molecules 2016, 21(10), 1319; https://doi.org/10.3390/molecules21101319 - 30 Sep 2016

Cited by 419 | Viewed by 18092

Abstract

A new theory for the study of the reactivity in Organic Chemistry, named Molecular Electron Density Theory (MEDT), is proposed herein. MEDT is based on the idea that while the electron density distribution at the ground state is responsible for physical and chemical [...] Read more.

A new theory for the study of the reactivity in Organic Chemistry, named Molecular Electron Density Theory (MEDT), is proposed herein. MEDT is based on the idea that while the electron density distribution at the ground state is responsible for physical and chemical molecular properties, as proposed by the Density Functional Theory (DFT), the capability for changes in electron density is responsible for molecular reactivity. Within MEDT, the reactivity in Organic Chemistry is studied through a rigorous quantum chemical analysis of the changes of the electron density as well as the energies associated with these changes along the reaction path in order to understand experimental outcomes. Studies performed using MEDT allow establishing a modern rationalisation and to gain insight into molecular mechanisms and reactivity in Organic Chemistry. Full article

(This article belongs to the Section Computational and Theoretical Chemistry)

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19 pages, 1388 KiB

Open AccessArticle

Fermentation Results and Chemical Composition of Agricultural Distillates Obtained from Rye and Barley Grains and the Corresponding Malts as a Source of Amylolytic Enzymes and Starch

by Maria Balcerek^*

, Katarzyna Pielech-Przybylska

, Urszula Dziekońska-Kubczak, Piotr Patelski and Ewelina Strąk

Department of Spirit and Yeast Technology, Institute of Fermentation Technology and Microbiology, Faculty of Biotechnology and Food Sciences, Lodz University of Technology, Wolczanska 171/173, Lodz 90-924, Poland

Molecules 2016, 21(10), 1320; https://doi.org/10.3390/molecules21101320 - 1 Oct 2016

Cited by 30 | Viewed by 7127

Abstract

The objective of this study was to determine the efficiency of rye and barley starch hydrolysis in mashing processes using cereal malts as a source of amylolytic enzymes and starch, and to establish the volatile profile of the obtained agricultural distillates. In addition, [...] Read more.

The objective of this study was to determine the efficiency of rye and barley starch hydrolysis in mashing processes using cereal malts as a source of amylolytic enzymes and starch, and to establish the volatile profile of the obtained agricultural distillates. In addition, the effects of the pretreatment method of unmalted cereal grains on the physicochemical composition of the prepared mashes, fermentation results, and the composition of the obtained distillates were investigated. The raw materials used were unmalted rye and barley grains, as well as the corresponding malts. All experiments were first performed on a semi-technical scale, and then verified under industrial conditions in a Polish distillery. The fermentable sugars present in sweet mashes mostly consisted of maltose, followed by glucose and maltotriose. Pressure-thermal treatment of unmalted cereals, and especially rye grains, resulted in higher ethanol content in mashes in comparison with samples subjected to pressureless liberation of starch. All agricultural distillates originating from mashes containing rye and barley grains and the corresponding malts were characterized by low concentrations of undesirable compounds, such as acetaldehyde and methanol. The distillates obtained under industrial conditions contained lower concentrations of higher alcohols (apart from 1-propanol) than those obtained on a semi-technical scale. Full article

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19 pages, 2157 KiB

Open AccessReview

Anti-Inflammatory Activity of Natural Products

by Abdullatif Azab¹, Ahmad Nassar² and Abed N. Azab^2,3,*

¹ Institute of Applied Research, The Galilee Society, P.O. Box 437, 20200 Shefa-Amr, Israel

² Department of Clinical Biochemistry and Pharmacology, Faculty of Health Sciences, Ben-Gurion University of the Negev, P.O. Box 653, 84105 Beer-Sheva, Israel

³ Department of Nursing, Faculty of Health Sciences, Ben-Gurion University of the Negev, P.O. Box 653, 84105 Beer-Sheva, Israel

Molecules 2016, 21(10), 1321; https://doi.org/10.3390/molecules21101321 - 1 Oct 2016

Cited by 340 | Viewed by 30352

Abstract

This article presents highlights of the published literature regarding the anti-inflammatory activities of natural products. Many review articles were published in this regard, however, most of them have presented this important issue from a regional, limited perspective. This paper summarizes the vast range [...] Read more.

This article presents highlights of the published literature regarding the anti-inflammatory activities of natural products. Many review articles were published in this regard, however, most of them have presented this important issue from a regional, limited perspective. This paper summarizes the vast range of review and research articles that have reported on the anti-inflammatory effects of extracts and/or pure compounds derived from natural products. Moreover, this review pinpoints some interesting traditionally used medicinal plants that were not investigated yet. Full article

(This article belongs to the Special Issue Natural Products and Inflammation)

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13 pages, 988 KiB

Open AccessReview

Natural and Synthetic Coumarins with Effects on Inflammation

by Gilbert Kirsch^1,*, Ahmed Bakr Abdelwahab^1,2

and Patrick Chaimbault¹

¹ SRSMC, UMR 7565, Groupe HeCRIN, ICPM, 1 boulevard Arago, 57070 Metz, France

² Chemistry of Natural Compounds Department, National Research Centre, El-Behoos St. 33, 12622 Dokki-Cairo, Egypt

Molecules 2016, 21(10), 1322; https://doi.org/10.3390/molecules21101322 - 2 Oct 2016

Cited by 110 | Viewed by 10019

Abstract

In this review, we will present the different aspects of coumarins and derivatives, from natural origins or synthetically prepared, and their action on inflammation. Coumarins and also furo- and pyranocoumarins are found in many different plants. These compounds are very often investigated for [...] Read more.

In this review, we will present the different aspects of coumarins and derivatives, from natural origins or synthetically prepared, and their action on inflammation. Coumarins and also furo- and pyranocoumarins are found in many different plants. These compounds are very often investigated for antioxidant properties. Other biological properties are also possible and anti-inflammation activity is one of these. As coumarins are also available quite easily via synthesis, natural ones can be prepared this way but derivatives with special substituents are also feasible. A review on the same topic appeared in 2004 and our contribution will take into account everything published since then. Full article

(This article belongs to the Special Issue Natural Products and Inflammation)

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21 pages, 753 KiB

Open AccessArticle

Anti-Inflammatory Effects of Aspalathus linearis and Cyclopia spp. Extracts in a UVB/Keratinocyte (HaCaT) Model Utilising Interleukin-1α Accumulation as Biomarker

by Tandeka Magcwebeba¹, Pieter Swart¹

, Sonja Swanevelder², Elizabeth Joubert^3,4

and Wentzel Gelderblom^1,5,*

¹ Department of Biochemistry, Stellenbosch University, Private Bag X1, Matieland (Stellenbosch) 7602, South Africa

² Biostatistics Unit, South African Medical Research Council, P.O. Box 19070, Tygerberg 7505, South Africa

³ Post-Harvest and Wine Technology Division, Agricultural Research Council (Infruitec-Nietvoorbij), Private Bag X5026, Stellenbosch 7599, South Africa

⁴ Department of Food Science, Stellenbosch University, Private Bag X1, Matieland (Stellenbosch) 7602, South Africa

⁵ Institute of Biomedical and Microbial Biotechnology, Cape Peninsula University of Technology, P.O. Box 1906, Bellville 7535, South Africa

Molecules 2016, 21(10), 1323; https://doi.org/10.3390/molecules21101323 - 2 Oct 2016

Cited by 46 | Viewed by 8825

Abstract

Ultraviolet B (UVB) radiation is one of the major predisposing risk factors of skin cancer. The anticancer and photoprotective effects of unoxidized rooibos (Aspalathus linearis) and honeybush (Cyclopia) herbal teas, containing high levels of dihydrochalones and xanthones, respectively, have [...] Read more.

Ultraviolet B (UVB) radiation is one of the major predisposing risk factors of skin cancer. The anticancer and photoprotective effects of unoxidized rooibos (Aspalathus linearis) and honeybush (Cyclopia) herbal teas, containing high levels of dihydrochalones and xanthones, respectively, have been demonstrated in skin cancer models in vivo. In the current study, the anti-inflammatory effects of methanol and aqueous extracts of these herbal teas were investigated in a UVB/HaCaT keratinocyte model with intracellular interleukin-1α (icIL-1α) accumulation as a biomarker. Extracts of green tea (Camellia sinensis) served as benchmark. Both extracts of green tea and rooibos, as well as the aqueous extract of C. intermedia, enhanced UVB-induced inhibition of cell viability, proliferation and induction of apoptosis, facilitating the removal of icIL-1α. The underlying mechanisms may involve mitochondrial dysfunction exhibiting pro-oxidant responses via polyphenol-iron interactions. The methanol extracts of honeybush, however, protected against UVB-induced reduction of cell growth parameters, presumably via antioxidant mechanisms that prevented the removal of highly inflamed icIL-1α-containing keratinocytes via apoptosis. The dual antioxidant and/or pro-oxidant role of the polyphenolic herbal tea constituents should be considered in developing preventive strategies against UVB-induced skin carcinogenesis. The indirect removal of UVB damaged keratinocytes by herbal tea extracts via apoptosis may find application in the prevention of photo-induced inflammation. Full article

(This article belongs to the Special Issue Natural Products and Inflammation)

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27 pages, 650 KiB

Open AccessArticle

Effect of Raw Material, Pressing and Glycosidase on the Volatile Compound Composition of Wine Made From Goji Berries

by Guanshen Yuan¹, Jie Ren¹, Xiaoyu Ouyang¹, Liying Wang², Mengze Wang², Xiaodong Shen², Bolin Zhang¹ and Baoqing Zhu^1,*

¹ Beijing Key Laboratory of Forestry Food Processing and Safety, Department of Food Science, College of Biological Sciences and Biotechnology, Beijing Forestry University, Beijing 100083, China

² Ningxia Senmiao Goji Technology Development Co. Ltd., Yinchuan, Ningxia 750000, China

Molecules 2016, 21(10), 1324; https://doi.org/10.3390/molecules21101324 - 2 Oct 2016

Cited by 23 | Viewed by 6139

Abstract

This study investigated the effect of raw material, pressing, and glycosidase on the aromatic profile of goji berry wine. The free-run and the pressed juice of dried and fresh goji berries were used for wine production, whereas glycosidase was applied to wine after [...] Read more.

This study investigated the effect of raw material, pressing, and glycosidase on the aromatic profile of goji berry wine. The free-run and the pressed juice of dried and fresh goji berries were used for wine production, whereas glycosidase was applied to wine after fermentation. Dried goji berry fermented wine exhibited much stronger fruity, floral, caramel, and herbaceous odors due to higher levels of esters, β-ionone and methionol. However, fresh berry fermented wine possessed stronger chemical notes due to higher levels of 4-ethylphenol. Pressing treatment reduced the fruity and caramel odors in these fermented wines, and fresh berry free-run juice fermented wine exhibited the least floral aroma. Glycosidase addition did not alter the aromatic composition of wines. The principal component analysis indicated that goji raw material played a primary role in differentiating the aromatic profiles of the wines due to the difference on the content of 20 esters, nine benzenes, eight aldehydes/ketones, three acids, two alcohols and six other volatiles. The content differences on isopentyl alcohol, styrene, benzyl alcohol, 1-octanol, (E)-5-decen-1-ol, 1-hexanol, and β-cyclocitral resulted in the segregation of the wines with and without the pressing treatment, especially for fresh berry fermented wine. Full article

(This article belongs to the Section Natural Products Chemistry)

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9 pages, 985 KiB

Open AccessArticle

Transformation of Tertiary Benzyl Alcohols into the Vicinal Halo-Substituted Derivatives Using N-Halosuccinimides

by Njomza Ajvazi^1,2 and Stojan Stavber^1,2,3,*

¹ Department of Physical and Organic Chemistry, Jožef Stefan Institute, Jamova 39, 1000 Ljubljana, Slovenia

² Jožef Stefan International Postgraduate School, Jamova 39, 1000 Ljubljana, Slovenia

³ Centre of Excellence for Integrated Approaches in Chemistry and Biology of Proteins CIPKeBiP (Seat at Jožef Stefan Institute), Jamova 39, 1000 Ljubljana, Slovenia

Molecules 2016, 21(10), 1325; https://doi.org/10.3390/molecules21101325 - 2 Oct 2016

Cited by 11 | Viewed by 8285

Abstract

The efficiency of direct conversion of tertiary alcohols bearing a β-hydrogen atom to vicinal halohydrins—chlorohydrins and bromohydrins—under green reaction conditions was tested preliminarily on model tertiary benzyl alcohols. Tertiary alcohols were successfully directly halogenated to vicinal halohydrins with N-halosuccinimide in aqueous media. [...] Read more.

The efficiency of direct conversion of tertiary alcohols bearing a β-hydrogen atom to vicinal halohydrins—chlorohydrins and bromohydrins—under green reaction conditions was tested preliminarily on model tertiary benzyl alcohols. Tertiary alcohols were successfully directly halogenated to vicinal halohydrins with N-halosuccinimide in aqueous media. The efficiency of the reaction in water was significantly improved in the presence of sodium dodecyl sulphate as the surfactant. Full article

(This article belongs to the Special Issue Organic Reaction in Green Solvents)

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27 pages, 667 KiB

Open AccessReview

Saponins from Chinese Medicines as Anticancer Agents

by Xiao-Huang Xu¹, Ting Li¹, Chi Man Vivienne Fong¹, Xiuping Chen¹, Xiao-Jia Chen¹, Yi-Tao Wang¹, Ming-Qing Huang^2,* and Jin-Jian Lu^1,*

¹ State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, China

² College of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou 350122, China

Molecules 2016, 21(10), 1326; https://doi.org/10.3390/molecules21101326 - 5 Oct 2016

Cited by 157 | Viewed by 10952

Abstract

Saponins are glycosides with triterpenoid or spirostane aglycones that demonstrate various pharmacological effects against mammalian diseases. To promote the research and development of anticancer agents from saponins, this review focuses on the anticancer properties of several typical naturally derived triterpenoid saponins (ginsenosides and [...] Read more.

Saponins are glycosides with triterpenoid or spirostane aglycones that demonstrate various pharmacological effects against mammalian diseases. To promote the research and development of anticancer agents from saponins, this review focuses on the anticancer properties of several typical naturally derived triterpenoid saponins (ginsenosides and saikosaponins) and steroid saponins (dioscin, polyphyllin, and timosaponin) isolated from Chinese medicines. These saponins exhibit in vitro and in vivo anticancer effects, such as anti-proliferation, anti-metastasis, anti-angiogenesis, anti-multidrug resistance, and autophagy regulation actions. In addition, related signaling pathways and target proteins involved in the anticancer effects of saponins are also summarized in this work. Full article

(This article belongs to the Special Issue Selected papers from 2nd International Symposium on Phytochemicals in Medicine and Food (2-ISPMF, Fuzhou, 2017))

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14 pages, 3133 KiB

Open AccessReview

Recent Advances in Dynamic Kinetic Resolution by Chiral Bifunctional (Thio)urea- and Squaramide-Based Organocatalysts

by Pan Li^1,2, Xinquan Hu¹, Xiu-Qin Dong^2,* and Xumu Zhang^2,3,*

¹ College of Chemical Engineering, Zhejiang University of Technology, Hangzhou 310014, Zhejiang, China

² College of Chemistry and Molecular Sciences, Wuhan University, Wuhan 430072, Hubei, China

³ Department of Chemistry, South University of Science and Technology of China, Shenzhen 518000, Guangdong, China

Molecules 2016, 21(10), 1327; https://doi.org/10.3390/molecules21101327 - 14 Oct 2016

Cited by 30 | Viewed by 10403

Abstract

The organocatalysis-based dynamic kinetic resolution (DKR) process has proved to be a powerful strategy for the construction of chiral compounds. In this feature review, we summarized recent progress on the DKR process, which was promoted by chiral bifunctional (thio)urea and squaramide catalysis via [...] Read more.

The organocatalysis-based dynamic kinetic resolution (DKR) process has proved to be a powerful strategy for the construction of chiral compounds. In this feature review, we summarized recent progress on the DKR process, which was promoted by chiral bifunctional (thio)urea and squaramide catalysis via hydrogen-bonding interactions between substrates and catalysts. A wide range of asymmetric reactions involving DKR, such as asymmetric alcoholysis of azlactones, asymmetric Michael–Michael cascade reaction, and enantioselective selenocyclization, are reviewed and demonstrate the efficiency of this strategy. The (thio)urea and squaramide catalysts with dual activation would be efficient for more unmet challenges in dynamic kinetic resolution. Full article

(This article belongs to the Collection Recent Advances in Organocatalysis)

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37 pages, 12671 KiB

Open AccessReview

HPLC Separation of Diastereomers: Chiral Molecular Tools Useful for the Preparation of Enantiopure Compounds and Simultaneous Determination of Their Absolute Configurations

by Nobuyuki Harada

Institute of Multidisciplinary Research for Advanced Materials, Tohoku University, 2-1-1 Katahira, Aoba, Sendai 980-8577, Japan

Molecules 2016, 21(10), 1328; https://doi.org/10.3390/molecules21101328 - 4 Oct 2016

Cited by 18 | Viewed by 10669

Abstract

To obtain enantiopure compounds, the so-called chiral high performance liquid chromatography (HPLC) method, i.e., HPLC using a chiral stationary phase, is very useful, as reviewed in the present Special Issue. On the other hand, normal HPLC (on silica gel) separation of diastereomers is [...] Read more.

To obtain enantiopure compounds, the so-called chiral high performance liquid chromatography (HPLC) method, i.e., HPLC using a chiral stationary phase, is very useful, as reviewed in the present Special Issue. On the other hand, normal HPLC (on silica gel) separation of diastereomers is also useful for the preparation of enantiopure compounds and also for the simultaneous determination of their absolute configurations (ACs). The author and coworkers have developed some chiral molecular tools, e.g., camphorsultam dichlorophthalic acid (CSDP acid), 2-methoxy-2-(1-naphthyl)propionic acid (MαNP acid), and others suitable for this purpose. For example, a racemic alcohol is esterified with (S)-(+)-MαNP acid, yielding diastereomeric esters, which are easily separable by HPLC on silica gel. The ACs of the obtained enantiopure MαNP esters can be determined by the ¹H-NMR diamagnetic anisotropy method. In addition, MαNP or CSDP esters have a high probability of giving single crystals suitable for X-ray crystallography. From the X-ray Oak Ridge thermal ellipsoid plot (ORTEP) drawing, the AC of the alcohol part can be unambiguously determined because the AC of the acid part is already known. The hydrolysis of MαNP or CSDP esters yields enantiopure alcohols with the established ACs. The mechanism and application examples of these methods are explained. Full article

(This article belongs to the Special Issue Chromatographic Separation of Enantiomers: Commemorative Issue in Honor of Professor Stig Allenmark on the Occasion of His 80th Birthday)

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8 pages, 433 KiB

Open AccessCommunication

Quantitative Determination of 3-O-Acetyl-11-Keto-βBoswellic Acid (AKBA) and Other Boswellic Acids in Boswellia sacra Flueck (syn. B. carteri Birdw) and Boswellia serrata Roxb

by Giuseppe Mannino¹

, Andrea Occhipinti^1,2 and Massimo E. Maffei^1,2,*

¹ Biosfered S.r.l., Innovation Centre, Academic Spin-Off of the University of Turin, Via Quarello 15/A, Turin 10135, Italy

² Department of Life Sciences and Systems Biology, Innovation Centre, University of Turin, Via Quarello 15/A, Turin 10135, Italy

Molecules 2016, 21(10), 1329; https://doi.org/10.3390/molecules21101329 - 6 Oct 2016

Cited by 66 | Viewed by 10642

Abstract

Boswellia serrata and Boswellia sacra (syn. B. carteri) are important medicinal plants widely used for their content of bioactive lipophilic triterpenes. The qualitative and quantitative determination of boswellic acids (BAs) is important for their use in dietary supplements aimed to provide a support [...] Read more.

Boswellia serrata and Boswellia sacra (syn. B. carteri) are important medicinal plants widely used for their content of bioactive lipophilic triterpenes. The qualitative and quantitative determination of boswellic acids (BAs) is important for their use in dietary supplements aimed to provide a support for osteoarthritic and inflammatory diseases. We used High Performance Liquid Chromatography (HPLC)-Diode Array Detector (DAD) coupled to ElectroSpray Ionization and tandem Mass Spectrometry (ESI-MS/MS) for the qualitative and quantitative determination of BAs extracted from the gum resins of B. sacra and B. serrata. Limit of detection (LOD), limit of quantification (LOQ), and Matrix Effect were assessed in order to validate quantitative data. Here we show that the BAs quantitative determination was 491.20 g·kg−1 d. wt (49%) in B. sacra and 295.25 g·kg−1 d. wt (30%) in B. serrata. Lower percentages of BAs content were obtained when BAs were expressed on the gum resin weight (29% and 16% for B. sacra and B. serrata, respectively). The content of Acetyl-11-Keto-β-Boswellic Acid (AKBA) was higher in B. sacra (70.81 g·kg−1 d. wt; 7%) than in B. serrata (7.35 g·kg−1 d. wt; 0.7%). Our results show that any claim of BAs content in either B. sacra or B. serrata gum resins equal to or higher than 70% or AKBA contents of 30% are simply unrealistic or based on a wrong quantitative determination. Full article

(This article belongs to the Collection Triterpenes and Triterpenoids)

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7 pages, 3761 KiB

Open AccessCommunication

Synthesis of Thioethers by InI₃-Catalyzed Substitution of Siloxy Group Using Thiosilanes

by Yoshihiro Nishimoto^1,*, Aya Okita², Akio Baba² and Makoto Yasuda^2,*

¹ Frontier Research Base for Global Young Researchers, Center for Open Innovation Research and Education(COiRE), Graduate School of Engineering, Osaka University, Osaka 565-0871, Japan

² Department of Applied Chemistry, Graduate School of Engineering, Osaka University, Osaka 565-0871, Japan

Molecules 2016, 21(10), 1330; https://doi.org/10.3390/molecules21101330 - 6 Oct 2016

Cited by 5 | Viewed by 6613

Abstract

The substitution of a siloxy group using thiosilanes smoothly occurred in the presence of InI₃ catalyst to yield the corresponding thioethers. InI₃ was a specifically effective catalyst in this reaction system, while other typical Lewis acids such as BF₃⋅OEt [...] Read more.

The substitution of a siloxy group using thiosilanes smoothly occurred in the presence of InI₃ catalyst to yield the corresponding thioethers. InI₃ was a specifically effective catalyst in this reaction system, while other typical Lewis acids such as BF₃⋅OEt₂, AlCl₃, and TiCl₄were ineffective. Various silyl ethers such as primary alkyl, secondary alkyl, tertiary alkyl, allylic, benzylic, and propargylic types were applicable. In addition, bulky OSitBuMe₂ and OSiiPr₃ groups, other than the OSiMe₃ group, were successfully substituted. The substitution reaction of enantiopure secondary benzylic silyl ether yielded the corresponding racemic thioether product, which suggested that the reaction of tertiary alkyl, secondary alkyl, benzylic, and propargylic silyl ethers would proceed via a S_N1 mechanism. Full article

(This article belongs to the Special Issue Advances in Silicon Chemistry)

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14 pages, 1152 KiB

Open AccessReview

Artemisinin and Its Derivatives as a Repurposing Anticancer Agent: What Else Do We Need to Do?

by Zhe Li^1,2,†

, Qin Li^2,†, Jun Wu², Manyuan Wang³ and Junxian Yu^1,*

¹ Department of Pharmacy, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China

² Cancer Center, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China

³ School of Traditional Chinese Medicine, Capital Medical University, Beijing 100069, China

^† These authors contributed equally to this work

Molecules 2016, 21(10), 1331; https://doi.org/10.3390/molecules21101331 - 7 Oct 2016

Cited by 72 | Viewed by 13039

Abstract

Preclinical investigation and clinical experience have provided evidence on the potential anticancer effect of artemisinin and its derivatives (ARTs) in the recent two decades. The major mechanisms of action of ARTs may be due to toxic-free radicals generated by an endoperoxide moiety, cell [...] Read more.

Preclinical investigation and clinical experience have provided evidence on the potential anticancer effect of artemisinin and its derivatives (ARTs) in the recent two decades. The major mechanisms of action of ARTs may be due to toxic-free radicals generated by an endoperoxide moiety, cell cycle arrest, induction of apoptosis, and inhibition of tumor angiogenesis. It is very promising that ARTs are expected to be a new class of antitumor drugs of wide spectrum due to their detailed information regarding efficacy and safety. For developing repurposed drugs, many other characteristics of ARTs should be studied, including through further investigations on possible new pathways of anticancer effects, exploration on efficient and specific drug delivery systems-especially crossing biological barriers, and obtaining sufficient data in clinical trials. The aim of this review is to highlight these achievements and propose the potential strategies to develop ARTs as a new class of cancer therapeutic agents. Full article

(This article belongs to the Special Issue Artemisinin: Against Malaria, Cancer and Viruses)

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19 pages, 3367 KiB

Open AccessArticle

Inhibition of Uterine Contractility by Thalidomide Analogs via Phosphodiesterase-4 Inhibition and Calcium Entry Blockade

by Eduardo Fernández-Martínez^1,*

, Héctor Ponce-Monter¹, Luis E. Soria-Jasso¹, Mario I. Ortiz¹, José-Antonio Arias-Montaño², Guillermo Barragán-Ramírez³ and Cynthia Mayén-García¹

¹ Centro de Investigación en Biología de la Reproducción, Área Académica de Medicina del Instituto de Ciencias de la Salud, Universidad Autónoma del Estado de Hidalgo, Pachuca 42090, Hidalgo, México

² Departamento de Fisiología, Biofísica y Neurociencias, Centro de Investigación y de Estudios Avanzados del IPN, Apdo. Postal 14-740, México City 07360, México

³ Hospital General de los SSH, Pachuca 42070, Hidalgo, México

Molecules 2016, 21(10), 1332; https://doi.org/10.3390/molecules21101332 - 7 Oct 2016

Cited by 16 | Viewed by 6942

Abstract

Uterine relaxation is crucial during preterm labor. Phosphodiesterase-4 (PDE-4) inhibitors have been proposed as tocolytics. Some thalidomide analogs are PDE-4 inhibitors. The aim of this study was to assess the uterus-relaxant properties of two thalidomide analogs, methyl
3-(4-nitrophthalimido)-3-(3,4-dimethoxyphenyl)-propanoate (4NO2PDPMe) and methyl
3-(4-aminophthalimido)-3-(3,4-dimethoxyphenyl)-propanoate (4APDPMe) [...] Read more.

Uterine relaxation is crucial during preterm labor. Phosphodiesterase-4 (PDE-4) inhibitors have been proposed as tocolytics. Some thalidomide analogs are PDE-4 inhibitors. The aim of this study was to assess the uterus-relaxant properties of two thalidomide analogs, methyl
3-(4-nitrophthalimido)-3-(3,4-dimethoxyphenyl)-propanoate (4NO2PDPMe) and methyl
3-(4-aminophthalimido)-3-(3,4-dimethoxyphenyl)-propanoate (4APDPMe) and were compared to rolipram in functional studies of spontaneous phasic, K⁺-induced tonic, and Ca²⁺-induced contractions in isolated pregnant human myometrial tissues. The accumulation of cAMP was quantified in HeLa cells. The presence of PDE-4B2 and phosphorylated myosin light-chain (pMLC), in addition to the effect of thalidomide analogs on oxytocin-induced pMLC, were assessed in human uterine myometrial cells (UtSMCs). Thalidomide analogs had concentration-dependent inhibitory effects on spontaneous and tonic contractions and inhibited Ca²⁺-induced responses. Tonic contraction was equipotently inhibited by 4APDPMe and rolipram (IC₅₀ = 125 ± 13.72 and 98.45 ± 8.86 µM, respectively). Rolipram and the thalidomide analogs inhibited spontaneous and tonic contractions equieffectively. Both analogs increased cAMP accumulation in a concentration-dependent manner (p < 0.05) and induced changes in the subcellular localization of oxytocin-induced pMLC in UtSMCs. The inhibitory effects of thalidomide analogs on the contractions of pregnant human myometrium tissue may be due to their PDE-4 inhibitory effect and novel mechanism as calcium-channel blockers. Full article

(This article belongs to the Section Medicinal Chemistry)

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13 pages, 842 KiB

Open AccessArticle

Relationship between the Ingestion of a Polyphenol-Rich Drink, Hepcidin Hormone, and Long-Term Training

by Débora Villaño^1,†, Cristina Vilaplana^1,†, Sonia Medina^1,*, Francisco Algaba-Chueca¹

, Roberto Cejuela-Anta², Jose Miguel Martínez-Sanz²

, Federico Ferreres¹ and Angel Gil-Izquierdo^1,*

¹ Department of Food Science and Technology, CEBAS-CSIC, Campus de Espinardo 25, Espinardo, Murcia 30100, Spain

² Faculty of Education, University of Alicante, Campus de Sant Vicent del Raspeig, Alicante 03690, Spain

^† These authors contribute equally to this work.

Molecules 2016, 21(10), 1333; https://doi.org/10.3390/molecules21101333 - 8 Oct 2016

Cited by 18 | Viewed by 5938

Abstract

The effects of polyphenol-rich foods on the iron status of athletes, as well as the effect of physical training on the hormone hepcidin, implicated in iron metabolism, are not clear. We investigated the influence on iron metabolism of a long-term training intervention of [...] Read more.

The effects of polyphenol-rich foods on the iron status of athletes, as well as the effect of physical training on the hormone hepcidin, implicated in iron metabolism, are not clear. We investigated the influence on iron metabolism of a long-term training intervention of 120 days, measuring the hepcidin concentration in the plasma of 16 elite triathletes, and the effect of the ingestion of 200 mL of either aronia-citrus juice or a placebo drink for 45 days, in a crossover design. The highest plasma hepcidin concentrations were observed at the beginning of the study (116 ± 63 nM) and levels steadily decreased until the end of the intervention (final value 10 ± 7.5 nM). Long-term training might reduce inflammation and, hence, could be responsible for the decrease in hepcidin in triathletes. Polyphenols from aronia-citrus juice did not interfere in iron absorption, as we did not observe significant differences between the intake of the placebo drink or juice with regard to hepcidin levels. Further studies are required to ascertain the time and conditions necessary to restore hepcidin levels, which reflect the iron status of triathletes. Full article

(This article belongs to the Special Issue New Frontiers on the Metabolism, Bioavailability and Health Effects of Phenolic Compounds)

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16 pages, 2813 KiB

Open AccessArticle

Targeted Delivery of siRNA to Transferrin Receptor Overexpressing Tumor Cells via Peptide Modified Polyethylenimine

by Yuran Xie¹, Bryan Killinger^1,2, Anna Moszczynska¹ and Olivia M. Merkel^1,3,*

¹ Department of Pharmaceutical Sciences, Wayne State University, 259 Mack Ave, Detroit, MI 48201, USA

² Van Andel Institute, Grand Rapids, MI 49503, USA

³ Department of Pharmacy, Ludwig-Maximilians Universität München, Butenandtstr. 5-13 (Haus B), D 81377 Munich, Germany

Molecules 2016, 21(10), 1334; https://doi.org/10.3390/molecules21101334 - 10 Oct 2016

Cited by 41 | Viewed by 9735

Abstract

The use of small interference RNA (siRNA) to target oncogenes is a promising treatment approach for cancer. However, siRNA cancer therapies are hindered by poor delivery of siRNA to cancer cells. Transferrin receptor (TfR) is overexpressed in many types of tumor cells and [...] Read more.

The use of small interference RNA (siRNA) to target oncogenes is a promising treatment approach for cancer. However, siRNA cancer therapies are hindered by poor delivery of siRNA to cancer cells. Transferrin receptor (TfR) is overexpressed in many types of tumor cells and therefore is a potential target for the selective delivery of siRNA to cancer cells. Here, we used the TfR binding peptide HAIYPRH (HAI peptide) conjugated to cationic polymer branched polyethylenimine (bPEI), optimized the coupling strategy, and the TfR selective delivery of siRNA was evaluated in cells with high (H1299) and low TfR expression (A549 and H460). The HAI-bPEI conjugate exhibited chemico-physical properties in terms of size, zeta-potential, and siRNA condensation efficiency similar to unmodified bPEI. Confocal microscopy and flow cytometry results revealed that HAI-bPEI selectively delivered siRNA to H1299 cells compared with A549 or H460 cells. Moreover, HAI-bPEI achieved more efficient glyceraldehyde 3-phosphate dehydrogenase (GAPDH) gene knockdown in H1299 cells compared with bPEI alone. However, despite optimization of the targeting peptide and coupling strategy, HAI-bPEI can only silence reporter gene enhanced green fluorescent protein (eGFP) at the protein level when chloroquine is present, indicating that further optimization of the conjugate is required. In conclusion, the HAI peptide may be useful to target TfR overexpressing tumors in targeted gene and siRNA delivery approaches. Full article

(This article belongs to the Special Issue Nucleic Acid-based Drug)

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14 pages, 2395 KiB

Open AccessArticle

Optimization Extraction, Preliminary Characterization and Antioxidant Activities of Polysaccharides from Semen Juglandis

by Xueyong Ren^1,*

, Liang He², Yanbin Wang² and Junwen Cheng²

¹ College of Materials Science and Technology, Beijing Forestry University, Beijing 100083, China

² Key Laboratory of Biological and Chemical Utilization of Zhejiang Forest Resources, Department of Forest Foods, Zhejiang Forestry Academy, Hangzhou 310023, China

Molecules 2016, 21(10), 1335; https://doi.org/10.3390/molecules21101335 - 9 Oct 2016

Cited by 9 | Viewed by 4602

Abstract

The optimization extraction process, preliminary characterization and antioxidant activities of polysaccharides from Semen Juglandis (SJP) were studied in this paper. Based on the Box-Behnken experimental design and response surface methodology, the optimal extraction conditions for the SJP extraction were obtained as follows: temperature [...] Read more.

The optimization extraction process, preliminary characterization and antioxidant activities of polysaccharides from Semen Juglandis (SJP) were studied in this paper. Based on the Box-Behnken experimental design and response surface methodology, the optimal extraction conditions for the SJP extraction were obtained as follows: temperature 88 °C, extraction time 125 min and ratio of liquid to solid 31 mL/g. Under these conditions, experimental extraction yield of SJP was (5.73 ± 0.014)% (n = 5), similar to the predicted value of 5.78%. Furtherly, the purified SJP obtained from SJP extract by DEAE-52 and Sephacryl S-100 chromatography was analyzed to be rhamnose, galacturonic acid, galactose, arabinose and fucose in the molar ratio of 1:6.34:1.38:3.21:1.56. And the weight-average molecular weight and radius of gyration of the purified SJP in 0.1 M NaCl were determined to be 2.76 × 10⁴ g/mol and 122 nm by SEC-MALLS, respectively. More importantly, it exhibited appreciable antioxidant activities compared to the standard Vc, such as DPPH radical scavenging activity (IC₅₀ 0.21 mg/mL), strong reducing power, ABTS radical scavenging activity (IC₅₀ 0.29 mg/mL), and hydroxyl radical scavenging activity (IC₅₀ 0.38 mg/mL). These results indicate that SJP may be useful for developing functional health products or natural antioxidant. Full article

(This article belongs to the Section Natural Products Chemistry)

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12 pages, 1707 KiB

Open AccessReview

The Potential Mechanisms of Berberine in the Treatment of Nonalcoholic Fatty Liver Disease

by Xiaopeng Zhu^1,2, Hua Bian^1,2,* and Xin Gao^1,2

¹ Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, Shanghai 200032, China

² Institute of Metabolic Disease, Fudan University, Shanghai 200032, China

Molecules 2016, 21(10), 1336; https://doi.org/10.3390/molecules21101336 - 14 Oct 2016

Cited by 57 | Viewed by 15914

Abstract

Nonalcoholic fatty liver disease (NAFLD) is a globally observed metabolic disease with high prevalence both in adults and children. However, there is no efficient medication available yet. Increased evidence indicates that berberine (BBR), a natural plant product, has beneficial effects on NAFLD, though [...] Read more.

Nonalcoholic fatty liver disease (NAFLD) is a globally observed metabolic disease with high prevalence both in adults and children. However, there is no efficient medication available yet. Increased evidence indicates that berberine (BBR), a natural plant product, has beneficial effects on NAFLD, though the mechanisms are not completely known. In this review, we briefly summarize the pathogenesis of NAFLD and factors that influence the progression of NAFLD, and focus on the potential mechanisms of BBR in the treatment of NAFLD. Increase of insulin sensitivity, regulation of adenosine monophosphate-activated protein kinase (AMPK) pathway, improvement of mitochondrial function, alleviation of oxidative stress, LDLR mRNA stabilization, and regulation of gut microenvironment are the major targets of BBR in the treatment of NAFLD. Additionally, reduction of proprotein convertase subtilisin/kexin 9 (PCSK9) expression and DNA methylation are also involved in pharmacological mechanisms of berberine in the treatment of NAFLD. The immunologic mechanism of BBR in the treatment of NAFLD, development of berberine derivative, drug combinations, delivery routes, and drug dose can be considered in the future research. Full article

(This article belongs to the Special Issue Natural Products and Chronic Diseases)

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17 pages, 4913 KiB

Open AccessArticle

Synthesis of Pyrazole-Thiobarbituric Acid Derivatives: Antimicrobial Activity and Docking Studies

by Yaseen A. M. M. Elshaier¹, Assem Barakat^2,3,*

, Bander M. Al-Qahtany², Abdullah Mohammed Al-Majid² and Mohamed H. Al-Agamy^4,5

¹ Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Al-Azhar University, Assuit 71524, Egypt

² Department of Chemistry, College of Science, King Saud University, P. O. Box 2455, Riyadh-11451, Saudi Arabia

³ Department of Chemistry, Faculty of Science, Alexandria University, P. O. Box 426, Ibrahimia, Alexandria 21321, Egypt

⁴ Microbiology and Immunology Department, Faculty of Pharmacy, Al-Azhar University, Cairo 11884, Egypt

⁵ Division of Microbiology, Pharmaceutics Department, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia

Molecules 2016, 21(10), 1337; https://doi.org/10.3390/molecules21101337 - 9 Oct 2016

Cited by 28 | Viewed by 6762

Abstract

A one-pot reaction was described that results in various pyrazole-thiobarbituric acid derivatives as new pharmacophore agents. These new heterocycles were synthesized in high yields with a broad substrate scope under mild reaction conditions in water mediated by NHEt₂. The molecular structures [...] Read more.

A one-pot reaction was described that results in various pyrazole-thiobarbituric acid derivatives as new pharmacophore agents. These new heterocycles were synthesized in high yields with a broad substrate scope under mild reaction conditions in water mediated by NHEt₂. The molecular structures of the synthesized compounds were assigned based on different spectroscopic techniques. The new compounds were evaluated for their antibacterial and antifungal activity. Compounds 4h and 4l were the most active compounds against C. albicans with MIC = 4 µg/L. Compound 4c exhibited the best activity against S. aureus and E. faecalis with MIC = 16 µg/L. However, compounds 4l and 4o were the most active against B. subtilis with MIC = 16 µg/L. Molecular docking studies for the final compounds and standard drugs were performed using the OpenEye program. Full article

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10 pages, 1531 KiB

Open AccessArticle

Design, Synthesis and Evaluation of Novel Tacrine-Ferulic Acid Hybrids as Multifunctional Drug Candidates against Alzheimer’s Disease

by Yingbo Fu¹, Yu Mu², Hui Lei², Pu Wang², Xin Li¹, Qiao Leng¹, Li Han², Xiaodan Qu², Zhanyou Wang^1,* and Xueshi Huang^1,2,*

¹ Laboratory of Metabolic Disease Research and Drug Development, China Medical University, Shenyang 110001, China

² Institute of Microbial Pharmaceuticals, College of Life and Health Sciences, Northeastern University, Shenyang 110819, China

Molecules 2016, 21(10), 1338; https://doi.org/10.3390/molecules21101338 - 11 Oct 2016

Cited by 29 | Viewed by 6462

Abstract

Five novel tacrine-ferulic acid hybrid compounds (8a–e) were synthesized and their structures were identified on the basis of a detailed spectroscopic analysis. The activities of inhibiting acetyl cholinesterase (AChE) and butyryl cholinesterase (BuChE), reducing self-induced β-amyloid (Aβ) aggregation and [...] Read more.

Five novel tacrine-ferulic acid hybrid compounds (8a–e) were synthesized and their structures were identified on the basis of a detailed spectroscopic analysis. The activities of inhibiting acetyl cholinesterase (AChE) and butyryl cholinesterase (BuChE), reducing self-induced β-amyloid (Aβ) aggregation and chelating Cu²⁺ were evaluated in vitro. Among them, 8c and 8d displayed the higher selectivity in inhibiting AChE over BuChE. Moreover, 8d also showed dramatic inhibition of self-Aβ aggregation, activity of chelating Cu²⁺ and activity against Aβ-induced neurotoxicity in Neuro-2A cells. Full article

(This article belongs to the Section Medicinal Chemistry)

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15 pages, 5095 KiB

Open AccessArticle

Thymol Mitigates Cadmium Stress by Regulating Glutathione Levels and Reactive Oxygen Species Homeostasis in Tobacco Seedlings

by Xiefeng Ye^1,†, Tianxiao Ling^1,†, Yanfeng Xue^2,†, Cunfa Xu³, Wei Zhou⁴, Liangbin Hu⁴, Jian Chen^5,6,* and Zhiqi Shi^5,6,*

¹ College of Tobacco Science, Henan Agricultural University, Zhengzhou 450002, China

² Nanjing Yangzi Modern Agriculture Investment and Development Co. Ltd., Nanjing 211899, China

³ Central Laboratory, Jiangsu Academy of Agricultural Science, Nanjing 210014, China

⁴ Department of Food Science, Henan Institute of Science and Technology, Xinxiang 453003, China

⁵ Institute of Food Quality and Safety, Jiangsu Academy of Agricultural Sciences, Nanjing 210014, China

⁶ Key Laboratory of Food Quality and Safety of Jiangsu Province-State Key Laboratory Breeding Base, Jiangsu Provincial Department of Agriculture and Forestry, Nanjing 210014, China

^† These authors contribute equally to this work.

Molecules 2016, 21(10), 1339; https://doi.org/10.3390/molecules21101339 - 14 Oct 2016

Cited by 43 | Viewed by 5452

Abstract

Thymol is a famous plant-derived compound that has been widely used in pharmacy due to its antioxidant and antimicrobial properties. However, the modulation of intrinsic plant physiology by thymol remains unclear. It is a significant challenge to confer plant tolerance to Cd (cadmium) [...] Read more.

Thymol is a famous plant-derived compound that has been widely used in pharmacy due to its antioxidant and antimicrobial properties. However, the modulation of intrinsic plant physiology by thymol remains unclear. It is a significant challenge to confer plant tolerance to Cd (cadmium) stress. In the present study physiological, histochemical, and biochemical methods were applied to investigate thymol-induced Cd tolerance in tobacco (Nicotiana tabacum) seedlings. Thymol was able to alleviate Cd-induced growth inhibition of tobacco seedlings in both dose- and time-dependent manners. Both histochemical detection and in-tube assays suggested that thymol treatment blocked Cd-induced over-generation of reactive oxygen species (ROS), lipid peroxidation, and loss of membrane integrity in both leaves and roots. Thymol decreased Cd-induced cell death that was indicated in vivo by propidium iodide (PI) and trypan blue, respectively. Thymol stimulated glutathione (GSH) biosynthesis by upregulating the expression of γ-glutamylcysteine synthetase 1 (GSH1) in Cd-treated seedlings, which may contribute to the alleviation of Cd-induced oxidative injury. In situ fluorescent detection of intracellular Cd²⁺ revealed that thymol significantly decreased free Cd²⁺ in roots, which could be explained by the thymol-stimulated GSH biosynthesis and upregulation of the expression of phyochelatin synthase 1 (PCS1). Taken together, these results suggested that thymol has great potential to trigger plant resistant responses to combat heavy metal toxicity, which may help our understanding of the mechanism for thymol-modulated cell metabolic pathways in response to environmental stimuli. Full article

(This article belongs to the Section Natural Products Chemistry)

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12 pages, 2266 KiB

Open AccessArticle

A High Content Screening Assay to Identify Compounds with Anti-Epithelial-Mesenchymal Transition Effects from the Chinese Herbal Medicine Tong-Mai-Yang-Xin-Wan

by Ningning Liu¹, Lailai Li¹, Xin Zhu², Zhiqiang Ling², Jianguo Feng², Ying Hu³, Yi Wang¹, Lijun Mou^3,* and Yi Wang^4,*

¹ TCM Research Center, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China

² Zhejiang Cancer Research Institute, Zhejiang Cancer Hospital, Hangzhou 310022, China

³ Department of Nephrology, The Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310029, China

⁴ College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China

Molecules 2016, 21(10), 1340; https://doi.org/10.3390/molecules21101340 - 10 Oct 2016

Cited by 12 | Viewed by 8358

Abstract

Chronic kidney disease (CKD) is a worldwide health problem with growing prevalence in developing countries. Renal tubular epithelial-mesenchymal transition (EMT) is a critical step and key factor in the development of this condition. Renal tubulointerstitial fibrosis is a basic pathological change at the [...] Read more.

Chronic kidney disease (CKD) is a worldwide health problem with growing prevalence in developing countries. Renal tubular epithelial-mesenchymal transition (EMT) is a critical step and key factor in the development of this condition. Renal tubulointerstitial fibrosis is a basic pathological change at the later stages of the disease. Therefore, blocking the development of EMT could be a critical factor in curing CKD. We have established a cell-based high-content screening (HCS) method to identify inhibitors of EMT in human proximal tubular epithelial (HK-2) cells by automatic acquisition and processing of dual-fluorescent labeled images. With the aid of chromatographic separation and mass spectrometry, we achieved the rapid and reliable screening of active compounds from the Chinese herbal medicine Tong-Mai-Yang-Xin-Wan (TMYX) for treating EMT. Five fractions were found to exert anti-EMT activity and were further identified by liquid chromatography coupled with tandem mass spectrometry. Glycyrrhizic acid, glyasperin A, and licorisoflavan A were found to inhibit EMT. The proposed approach was successfully applied to screen active compounds from TMYX on TGF-β1-stimulated HK-2 cells and may offer a new means for identifying lead compounds for treating EMT from registered Chinese herbal medicines. Full article

(This article belongs to the Collection Herbal Medicine Research)

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12 pages, 1869 KiB

Open AccessArticle

Resveratrol Ameliorates the Depressive-Like Behaviors and Metabolic Abnormalities Induced by Chronic Corticosterone Injection

by Yu-Cheng Li^*

, Ya-Min Liu, Ji-Duo Shen, Jun-Jie Chen, Yang-Yi Pei and Xiao-Yan Fang^*

College of Pharmacy, Henan University of Traditional Chinese Medicine, Zhengzhou 450046, China

Molecules 2016, 21(10), 1341; https://doi.org/10.3390/molecules21101341 - 13 Oct 2016

Cited by 43 | Viewed by 7431

Abstract

Chronic glucocorticoid exposure is known to cause depression and metabolic disorders. It is critical to improve abnormal metabolic status as well as depressive-like behaviors in patients with long-term glucocorticoid therapy. This study aimed to investigate the effects of resveratrol on the depressive-like behaviors [...] Read more.

Chronic glucocorticoid exposure is known to cause depression and metabolic disorders. It is critical to improve abnormal metabolic status as well as depressive-like behaviors in patients with long-term glucocorticoid therapy. This study aimed to investigate the effects of resveratrol on the depressive-like behaviors and metabolic abnormalities induced by chronic corticosterone injection. Male ICR mice were administrated corticosterone (40 mg/kg) by subcutaneous injection for three weeks. Resveratrol (50 and 100 mg/kg), fluoxetine (20 mg/kg) and pioglitazone (10 mg/kg) were given by oral gavage 30 min prior to corticosterone administration. The behavioral tests showed that resveratrol significantly reversed the depressive-like behaviors induced by corticosterone, including the reduced sucrose preference and increased immobility time in the forced swimming test. Moreover, resveratrol also increased the secretion of insulin, reduced serum level of glucose and improved blood lipid profiles in corticosterone-treated mice without affecting normal mice. However, fluoxetine only reverse depressive-like behaviors, and pioglitazone only prevent the dyslipidemia induced by corticosterone. Furthermore, resveratrol and pioglitazone decreased serum level of glucagon and corticosterone. The present results indicated that resveratrol can ameliorate depressive-like behaviors and metabolic abnormalities induced by corticosterone, which suggested that the multiple effects of resveratrol could be beneficial for patients with depression and/or metabolic syndrome associated with long-term glucocorticoid therapy. Full article

(This article belongs to the Special Issue Improvements for Resveratrol Efficacy)

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13 pages, 1126 KiB

Open AccessArticle

Synthesis of Xylitan Derivatives and Preliminary Evaluation of in Vitro Trypanocidal Activity

by Paula Regina Elias¹, Gleicekelly Silva Coelho¹, Viviane Flores Xavier^1,2, Policarpo Ademar Sales Junior², Alvaro José Romanha², Silvane Maria Fonseca Murta², Claudia Martins Carneiro³, Nilton Soares Camilo⁴, Flaviane Francisco Hilário¹ and Jason Guy Taylor^1,*

¹ Chemistry Department, ICEB, Federal University of Ouro Preto, Campus Universitário Morro do Cruzeiro, 35400-000 Ouro Preto, MG, Brazil

² Centro de Pesquisas René Rachou, A Fundação Oswaldo Cruz/FIOCRUZ, 30190-002 Belo Horizonte, MG, Brazil

³ Immunopathology Laboratory, NUPEB, Federal University of Ouro Preto, Campus Universitário Morro do Cruzeiro, 35400-000 Ouro Preto-MG, Brazil

⁴ Instituto de Química, Universidade Estadual de Campinas, C.P. 6154, CEP. 13084-971 Campinas, SP, Brazil

Molecules 2016, 21(10), 1342; https://doi.org/10.3390/molecules21101342 - 10 Oct 2016

Cited by 13 | Viewed by 5457

Abstract

A series of novel xylitan derivatives derived from xylitol were synthesized using operationally simple procedures. A xylitan acetonide was the key intermediate used to prepare benzoate, arylsulfonate esters and 1,2,3-triazole derivatives of xylitan. These compounds were evaluated for their in vitro anti-Trypanosoma [...] Read more.

A series of novel xylitan derivatives derived from xylitol were synthesized using operationally simple procedures. A xylitan acetonide was the key intermediate used to prepare benzoate, arylsulfonate esters and 1,2,3-triazole derivatives of xylitan. These compounds were evaluated for their in vitro anti-Trypanosoma cruzi activity against trypomastigote and amastigote forms of the parasite in T. cruzi-infected cell lineages. Benznidazole was used as positive control against T. cruzi and cytotoxicity was determined in mammalian L929 cells. The arylsulfonate xylitan derivative bearing a nitro group displayed the best activity of all the compounds tested, and was slightly more potent than the reference drug benznidazole. The importance of the isopropylidene ketal moiety was established and the greater lipophilicity of these compounds suggests enhancement in cell penetration. Full article

(This article belongs to the Section Medicinal Chemistry)

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15 pages, 2657 KiB

Open AccessArticle

Modulation of Autophagy by a Thioxanthone Decreases the Viability of Melanoma Cells

by Raquel T. Lima^1,2,3,†, Diana Sousa^1,2,4,†, Ana M. Paiva⁵, Andreia Palmeira⁵, João Barbosa⁶, Madalena Pedro⁶, Madalena M. Pinto^5,7

, Emília Sousa^5,7

and M. Helena Vasconcelos^1,2,4,*

¹ i3S-Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Rua Alfredo Allen 208, 4200-135 Porto, Portugal

² Cancer Drug Resistance Group, IPATIMUP—Institute of Molecular Pathology and Immunology of the University of Porto, Rua Júlio Amaral de Carvalho, 45, 4200-135 Porto, Portugal

³ Department of Pathology, FMUP—Faculty of Medicine of the University of Porto, Alameda Prof. Hernâni Monteiro, 4200-319 Porto, Portugal

⁴ Laboratory of Microbiology, Department of Biological Sciences, FFUP—Faculty of Pharmacy, University of Porto, Rua de Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal

⁵ Laboratory of Organic and Pharmaceutical Chemistry, Department of Chemical Sciences, FFUP—Faculty of Pharmacy, University of Porto, Rua de Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal

⁶ CESPU, Instituto de Investigação e Formação Avançada em Ciências e Tecnologias da Saúde, IUCS—Instituto Universitário de Ciências da Saúde, Rua Central de Gandra 1317, 4585-116 Gandra, Portugal

⁷ CIIMAR/CIMAR—Centro Interdisciplinar de Investigação Marinha e Ambiental, Universidade do Porto, Terminal de Cruzeiros do Porto de Leixões, Avenida General Norton de Matos, S/N, 4450-208 Matosinhos, Portugal

^† These authors equally contributed to this work.

Molecules 2016, 21(10), 1343; https://doi.org/10.3390/molecules21101343 - 10 Oct 2016

Cited by 33 | Viewed by 6780

Abstract

(1) Background: Our previous studies unveiled the hit thioxanthone TXA1 as an inhibitor of P-glycoprotein (drug efflux pump) and of human tumor cells growth, namely of melanoma cells. Since TXA1 is structurally similar to lucanthone (an autophagy inhibitor and apoptosis inducer) and to [...] Read more.

(1) Background: Our previous studies unveiled the hit thioxanthone TXA1 as an inhibitor of P-glycoprotein (drug efflux pump) and of human tumor cells growth, namely of melanoma cells. Since TXA1 is structurally similar to lucanthone (an autophagy inhibitor and apoptosis inducer) and to N¹⁰-substituted phenoxazines (isosteres of thioxanthones, and autophagy inducers), this study aimed at further assessing its cytotoxic mechanism and evaluating its potential as an autophagy modulator in A375-C5 melanoma cells; (2) Methods: Flow cytometry with propidium iodide (PI) for cell cycle profile analysis; Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, flow cytometry with Annexin V/PI labeling and Western blot for apoptosis analysis were conducted. A pharmacophore approach was used for mapping TXA1 onto pharmacophores for autophagy induction. Autophagy analyses included transmission electron microscopy for visualization of autophagic structures, fluorescence microscopy for observation of monodansylcadaverine (MDC) staining, pattern of LC3 expression in the cells and acridine orange staining, and Western blot for autophagic proteins expression; (3) Results: TXA1 induced autophagy of melanoma cells at the GI₅₀ concentration (3.6 μM) and apoptosis at twice that concentration. Following treatment with TXA1, autophagic structures were observed, together with the accumulation of autophagosomes and the formation of autophagolysosomes. An increase in LC3-II levels was also observed, which was reverted by 3-methyladenine (3-MA) (an early stage autophagy-inhibitor) but further increased by E-64d/pepstatin (late-stage autophagy inhibitors). Finally, 3-MA also reverted the effect of TXA1 in cellular viability; (4) Conclusion: TXA1 decreases the viability of melanoma cells by modulation of autophagy and may, therefore, serve as a lead compound for the development of autophagy modulators with antitumor activity. Full article

(This article belongs to the Collection Efficient Pharmaceutical and Chemical Approaches for Anticancer Therapy: Design, Preliminary Evaluations, and Further Developments)

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9 pages, 2024 KiB

Open AccessArticle

Picrotoxane Sesquiterpene Glycosides and a Coumarin Derivative from Coriaria nepalensis and Their Neurotrophic Activity

by Yuan-Yuan Wang, Jun-Mian Tian, Cheng-Chen Zhang

, Bo Luo and Jin-Ming Gao^*

Shaanxi Key Laboratory of Natural Products & Chemical Biology, College of Science, Northwest A&F University, Yangling 712100, Shaanxi, China

Molecules 2016, 21(10), 1344; https://doi.org/10.3390/molecules21101344 - 12 Oct 2016

Cited by 13 | Viewed by 5549

Abstract

Two picrotoxane sesquiterpene lactone glycosides, nepalactones A (1) and B (2), and one new coumarin, nepalarin (3), were isolated from the root barks of the poisonous plant Coriaria nepalensis. Their structures were elucidated via HRESIMS and [...] Read more.

Two picrotoxane sesquiterpene lactone glycosides, nepalactones A (1) and B (2), and one new coumarin, nepalarin (3), were isolated from the root barks of the poisonous plant Coriaria nepalensis. Their structures were elucidated via HRESIMS and 1D and 2D NMR spectroscopic analyses, and further verified via transformation methods. In addition, compounds 1–3 and five semisynthetic congeners (1a–e) were assayed for the activity to induce neurite outgrowth in rat pheochromocytoma (PC12) cells. As a result, nepalactone A derivative 1c and nepalarin (3) significantly enhanced nerve growth factor (NGF)-mediated neurite outgrowth in PC12 cells. Full article

(This article belongs to the Collection Bioactive Compounds)

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13 pages, 5848 KiB

Open AccessArticle

Ultraviolet B (UVB) Photosensitivities of Tea Catechins and the Relevant Chemical Conversions

by Meng Shi, Ying Nie, Xin-Qiang Zheng

, Jian-Liang Lu, Yue-Rong Liang

and Jian-Hui Ye^*

Tea Research Institute, Zhejiang University, Hangzhou 310058, China

Molecules 2016, 21(10), 1345; https://doi.org/10.3390/molecules21101345 - 10 Oct 2016

Cited by 39 | Viewed by 7977

Abstract

Ultraviolet B (UVB) photosensitivities of eight catechins were screened. In both water and ethanol, epicatechin (EC, 575 μM) and catechin (C, 575 μM) exhibited low photostabilities under 6 h UVB radiation with the generation of yellow photoproducts, while other catechins (epigallocatechin gallate, epigallocatechin, [...] Read more.

Ultraviolet B (UVB) photosensitivities of eight catechins were screened. In both water and ethanol, epicatechin (EC, 575 μM) and catechin (C, 575 μM) exhibited low photostabilities under 6 h UVB radiation with the generation of yellow photoproducts, while other catechins (epigallocatechin gallate, epigallocatechin, epicatechin gallate, gallocatechingallate, gallocatechin, catechin gallate) were relatively UVB-insensitive. Photoisomerization and photolysis were two important UVB-induced reactions to EC whereas photolysis was the dominant reaction for C. The influencing factors of time (2–10 h), solvent (water, ethanol) and substrate concentration (71.875–1150 μM) on UVB-induced chemical conversions of EC and C were investigated, and eight photoproducts were identified through ultra performance liquid chromatography-diode array detection-tandem mass spectrometry (UPLC-DAD-MS/MS) and ¹H nuclear magnetic resonance (¹H-NMR analysis). Photolysis reaction involved two pathways, including radical reaction and photo-induced electron transfer reaction. The 2,2-diphenylpicrylhydrazyl (DPPH) scavenging abilities of eight catechins did not change upon 6 h UVB irradiation. EC and C are photosensitive catechins among eight catechins causing deep color. Full article

(This article belongs to the Special Issue Polyphenols and Antioxidants–The Chemistry of Tea)

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11 pages, 3120 KiB

Open AccessArticle

Gallic Acid Content in Taiwanese Teas at Different Degrees of Fermentation and Its Antioxidant Activity by Inhibiting PKCδ Activation: In Vitro and in Silico Studies

by Teeradate Kongpichitchoke¹, Ming-Tzu Chiu², Tzou-Chi Huang³ and Jue-Liang Hsu^3,*

¹ Department of Agro-Industry, Assumption University, Bangkok 10240, Thailand

² Taiwan Tea Experiment Station, Council of Agriculture, Taoyuan 326, Taiwan

³ Department of Biological Science and Technology, National Pingtung University of Science and Technology, Pingtung 91201, Taiwan

Molecules 2016, 21(10), 1346; https://doi.org/10.3390/molecules21101346 - 12 Oct 2016

Cited by 28 | Viewed by 7546

Abstract

Teas can be classified according to their degree of fermentation, which has been reported to affect both the bioactive components in the teas and their antioxidative activity. In this study, four kinds of commercial Taiwanese tea at different degrees of fermentation, which include [...] Read more.

Teas can be classified according to their degree of fermentation, which has been reported to affect both the bioactive components in the teas and their antioxidative activity. In this study, four kinds of commercial Taiwanese tea at different degrees of fermentation, which include green (non-fermented), oolong (semi-fermented), black (fully fermented), and Pu-erh (post-fermented) tea, were profiled for catechin levels by using high performance liquid chromatography (HPLC). The result indicated that the gallic acid content in tea was directly proportional to the degree of fermentation in which the lowest and highest gallic acid content were 1.67 and 21.98 mg/g from green and Pu-erh tea, respectively. The antioxidative mechanism of the gallic acid was further determined by in vitro and in silico analyses. In vitro assays included the use of phorbol ester-induced macrophage RAW264.7 cell model for determining the inhibition of reactive oxygen species (ROS) production, and PKCδ and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunit (p47) activations. The results showed that only at a concentration of 5.00 μM could gallic acid significantly (p < 0.05) reduce ROS levels in phorbol ester-activated macrophages. Moreover, protein immunoblotting expressed similar results in which activations of PKCδ and p47 were only significantly (p < 0.05) attenuated by 5.00 μM treatment. Lastly, in silico experiments further revealed that gallic acid could block PKCδ activation by occupying the phorbol ester binding sites of the protein. Full article

(This article belongs to the Special Issue Catechins and Human Health: Current State of the Science)

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12 pages, 2521 KiB

Open AccessArticle

Evaluation of Hydrogel Suppositories for Delivery of 5-Aminolevulinic Acid and Hematoporphyrin Monomethyl Ether to Rectal Tumors

by Xuying Ye¹, Huijuan Yin^2,*

, Yu Lu², Haixia Zhang² and Han Wang²

¹ Cardiovascular Medicine, Tianjin First Center Hospital, Tianjin 300192, China

² Laser Medicine Laboratory, Institute of Biomedical Engineering, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300192, China

Molecules 2016, 21(10), 1347; https://doi.org/10.3390/molecules21101347 - 12 Oct 2016

Cited by 15 | Viewed by 6136

Abstract

We evaluated the potential utility of hydrogels for delivery of the photosensitizing agents 5-aminolevulinic acid (ALA) and hematoporphyrin monomethyl ether (HMME) to rectal tumors. Hydrogel suppositories containing ALA or HMME were administered to the rectal cavity of BALB/c mice bearing subcutaneous tumors of [...] Read more.

We evaluated the potential utility of hydrogels for delivery of the photosensitizing agents 5-aminolevulinic acid (ALA) and hematoporphyrin monomethyl ether (HMME) to rectal tumors. Hydrogel suppositories containing ALA or HMME were administered to the rectal cavity of BALB/c mice bearing subcutaneous tumors of SW837 rectal carcinoma cells. For comparison, ALA and HMME were also administered by three common photosensitizer delivery routes; local administration to the skin and intratumoral or intravenous injection. The concentration of ALA-induced protoporphyrin IX or HMME in the rectal wall, skin, and subcutaneous tumor was measured by fluorescence spectrophotometry, and their distribution in vertical sections of the tumor was measured using a fluorescence spectroscopy system. The concentration of ALA-induced protoporphyrin IX in the rectal wall after local administration of suppositories to the rectal cavity was 9.76-fold (1 h) and 5.8-fold (3 h) higher than in the skin after cutaneous administration. The maximal depth of ALA penetration in the tumor was ~3–6 mm at 2 h after cutaneous administration. Much lower levels of HMME were observed in the rectal wall after administration as a hydrogel suppository, and the maximal depth of tumor penetration was <2 mm after cutaneous administration. These data show that ALA more readily penetrates the mucosal barrier than the skin. Administration of ALA as an intrarectal hydrogel suppository is thus a potential delivery route for photodynamic therapy of rectal cancer. Full article

(This article belongs to the Special Issue Photodynamic Therapy)

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19 pages, 6875 KiB

Open AccessReview

Porphyrin-Based Metal-Organic Frameworks as Heterogeneous Catalysts in Oxidation Reactions

by Carla F. Pereira^1,2, Mário M. Q. Simões^2,*

, João P. C. Tomé^2,3 and Filipe A. Almeida Paz^1,*

¹ Department of Chemistry & CICECO–Aveiro Institute of Materials, University of Aveiro, 3810-193 Aveiro, Portugal

² Department of Chemistry & QOPNA, University of Aveiro, 3810-193 Aveiro, Portugal

³ CQE, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisboa, Portugal

Molecules 2016, 21(10), 1348; https://doi.org/10.3390/molecules21101348 - 12 Oct 2016

Cited by 89 | Viewed by 13982

Abstract

Porphyrin-based Metal-Organic Frameworks (Por-MOFs) constitute a special branch of the wide MOF family that has proven its own value and high potential in different applications. In this mini-review the application of these materials as catalysts in oxidation reactions is highlighted. Full article

(This article belongs to the Special Issue Phase-Transfer Catalysis)

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8 pages, 948 KiB

Open AccessArticle

Synthesis and Antifungal Activity against Fusarium oxysporum of Some Brassinin Analogs Derived from l-tryptophan: A DFT/B3LYP Study on the Reaction Mechanism

by Diego Quiroga^*

, Lili Dahiana Becerra, John Sadat-Bernal, Nathalia Vargas and Ericsson Coy-Barrera

Bioorganic Chemistry Laboratory, Facultad de Ciencias Básicas y Aplicadas, Universidad Militar Nueva Granada, Campus Nueva Granada, Cajicá 49300, Colombia

Molecules 2016, 21(10), 1349; https://doi.org/10.3390/molecules21101349 - 11 Oct 2016

Cited by 10 | Viewed by 6125

Abstract

An efficient methodology to obtain novel antifungal analogs of brassinin 1 is described. Starting from l-tryptophan 2, N,N′-dialkylthiourea 4, 4-[(1H-indol-3-yl)methylene]-2-sulfanylidene-1,3-thiazolidin-5-one 5 and alkyl (2S)-3-(1H-indol-3-yl)-2-{[(alkylsulfanyl)carbonothioyl]amino}propanoate 6 type compounds were obtained as main [...] Read more.

An efficient methodology to obtain novel antifungal analogs of brassinin 1 is described. Starting from l-tryptophan 2, N,N′-dialkylthiourea 4, 4-[(1H-indol-3-yl)methylene]-2-sulfanylidene-1,3-thiazolidin-5-one 5 and alkyl (2S)-3-(1H-indol-3-yl)-2-{[(alkylsulfanyl)carbonothioyl]amino}propanoate 6 type compounds were obtained as main products in different ratios depending on the reaction conditions via a tandem dithiocarbamate formation and Michael addition reaction. In order to understand the dependence of the reaction conditions on the mechanism pathway, a DFT/B3LYP study was performed. The results suggested the existence of competitive mechanistic routes which involve the presence of an ionic dithiocarbamate intermediate 9. Antifungal activities of all products were then evaluated against Fusarium oxysporum through mycelial growth inhibition using a microscale amended-medium assay. IC₅₀ values were thus determined for each compound. These results showed that 6-related compounds can be considered as promissory antifungal agents. Full article

(This article belongs to the Special Issue MCRs and Related One-Pot Organic Synthesis)

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14 pages, 1728 KiB

Open AccessArticle

Protective Effect of the Plant Extracts of Erythroxylum sp. against Toxic Effects Induced by the Venom of Lachesis muta Snake

by Eduardo Coriolano de Oliveira¹, Rodrigo Alves Soares Cruz², Nayanna De Mello Amorim¹, Marcelo Guerra Santos³, Luiz Carlos Simas Pereira Junior¹, Eladio Oswaldo Flores Sanchez⁴, Caio Pinho Fernandes⁵, Rafael Garrett⁶

, Leandro Machado Rocha⁷ and André Lopes Fuly^1,*

¹ Department of Molecular and Cellular Biology, Institute of Biology, Federal Fluminense University, Niterói 24020-141, RJ, Brazil

² Department of Biological and Health Sciences, Faculty of Pharmacy, Federal University of Amapá, Macapá 68903-419, AP, Brazil

³ Faculdade de Formação de Professores, University of the State of Rio de Janeiro, Rio de Janeiro 24435-005, RJ, Brazil

⁴ Laboratory of Biochemistry of Proteins from Animal Venoms, Research and Development Center, Ezequiel Dias Foundation, Belo Horizonte 30510-010, MG, Brazil

⁵ Laboratory of Phytopharmaceutical Nanobiotechnology, Department of Biological and Health Sciences, Federal University of Amapá, Macapá 68903-419, AP, Brazil

⁶ Mass Spectrometry Laboratory, Institute of Chemistry, Federal University of Rio de Janeiro, Rio de Janeiro 21941-598, RJ, Brazil

⁷ Department of Pharmaceutical Technology, Faculty of Pharmacy, Fluminense Federal University, Niterói 24210-346, RJ, Brazil

Molecules 2016, 21(10), 1350; https://doi.org/10.3390/molecules21101350 - 11 Oct 2016

Cited by 15 | Viewed by 5977

Abstract

Snake venoms are composed of a complex mixture of active proteins that induce toxic effects, such as edema, hemorrhage, and death. Lachesis muta has the highest lethality indices in Brazil. In most cases, antivenom fails to neutralize local effects, leading to disabilities in [...] Read more.

Snake venoms are composed of a complex mixture of active proteins that induce toxic effects, such as edema, hemorrhage, and death. Lachesis muta has the highest lethality indices in Brazil. In most cases, antivenom fails to neutralize local effects, leading to disabilities in victims. Thus, alternative treatments are under investigation, and plant extracts are promising candidates. The objective of this work was to investigate the ability of crude extracts, fractions, or isolated products of Erythroxylum ovalifolium and Erythroxylum subsessile to neutralize some toxic effects of L. muta venom. All samples were mixed with L. muta venom, then in vivo (hemorrhage and edema) and in vitro (proteolysis, coagulation, and hemolysis) assays were performed. Overall, crude extracts or fractions of Erythroxylum spp. inhibited (20%–100%) toxic effects of the venom, but products achieved an inhibition of 4%–30%. However, when venom was injected into mice before the plant extracts, hemorrhage and edema were not inhibited by the samples. On the other hand, an inhibition of 5%–40% was obtained when extracts or products were given before venom injection. These results indicate that the extracts or products of Erythroxylum spp. could be a promising source of molecules able to treat local toxic effects of envenomation by L. muta venom, aiding in the development of new strategies for antivenom treatment. Full article

(This article belongs to the Section Natural Products Chemistry)

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15 pages, 3442 KiB

Open AccessReview

Natural Dietary and Herbal Products in Anti-Obesity Treatment

by Nan-Nong Sun¹, Tsung-Yen Wu¹ and Chi-Fai Chau^1,2,*

¹ Department of Food Science and Biotechnology, National Chung Hsing University, Taichung 40227, Taiwan

² Agricultural Biotechnology Center, National Chung Hsing University, Taichung 40227, Taiwan

Molecules 2016, 21(10), 1351; https://doi.org/10.3390/molecules21101351 - 11 Oct 2016

Cited by 193 | Viewed by 19473

Abstract

The prevalence of overweight and obesity is on the rise around the world. Common comorbidities associated with obesity, particularly diabetes, hypertension, and heart disease have an impact on social and financial systems. Appropriate lifestyle and behavior interventions are still the crucial cornerstone to [...] Read more.

The prevalence of overweight and obesity is on the rise around the world. Common comorbidities associated with obesity, particularly diabetes, hypertension, and heart disease have an impact on social and financial systems. Appropriate lifestyle and behavior interventions are still the crucial cornerstone to weight loss success, but maintaining such a healthy lifestyle is extremely challenging. Abundant natural materials have been explored for their obesity treatment potential and widely used to promote the development of anti-obesity products. The weight loss segment is one of the major contributors to the overall revenue of the dietary supplements market. In this review, the anti-obesity effects of different dietary or herbal products, and their active ingredients and mechanisms of action against obesity will be discussed. Full article

(This article belongs to the Special Issue Natural Products in Anti-Obesity Therapy)

13 pages, 1823 KiB

Open AccessArticle

A Reliable Method for the Evaluation of the Anaphylactoid Reaction Caused by Injectable Drugs

by Fang Wang¹, Zebin Weng¹, Cunyu Li^1,2 and Guoping Peng^1,2,*

¹ School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China

² Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing 210023, China

Molecules 2016, 21(10), 1352; https://doi.org/10.3390/molecules21101352 - 12 Oct 2016

Cited by 7 | Viewed by 5515

Abstract

Adverse reactions of injectable drugs usually occur at first administration and are closely associated with the dosage and speed of injection. This phenomenon is correlated with the anaphylactoid reaction. However, up to now, study methods based on antigen detection have still not gained [...] Read more.

Adverse reactions of injectable drugs usually occur at first administration and are closely associated with the dosage and speed of injection. This phenomenon is correlated with the anaphylactoid reaction. However, up to now, study methods based on antigen detection have still not gained wide acceptance and single physiological indicators cannot be utilized to differentiate anaphylactoid reactions from allergic reactions and inflammatory reactions. In this study, a reliable method for the evaluation of anaphylactoid reactions caused by injectable drugs was established by using multiple physiological indicators. We used compound 48/80, ovalbumin and endotoxin as the sensitization agents to induce anaphylactoid, allergic and inflammatory reactions. Different experimental animals (guinea pig and nude rat) and different modes of administration (intramuscular, intravenous and intraperitoneal injection) and different times (15 min, 30 min and 60 min) were evaluated to optimize the study protocol. The results showed that the optimal way to achieve sensitization involved treating guinea pigs with the different agents by intravenous injection for 30 min. Further, seven related humoral factors including 5-HT, SC5b-9, Bb, C4d, IL-6, C3a and histamine were detected by HPLC analysis and ELISA assay to determine their expression level. The results showed that five of them, including 5-HT, SC5b-9, Bb, C4d and IL-6, displayed significant differences between anaphylactoid, allergic and inflammatory reactions, which indicated that their combination could be used to distinguish these three reactions. Then different injectable drugs were used to verify this method and the results showed that the chosen indicators exhibited good correlation with the anaphylactoid reaction which indicated that the established method was both practical and reliable. Our research provides a feasible method for the diagnosis of the serious adverse reactions caused by injectable drugs which could be used in the clinical practice. Full article

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16 pages, 6929 KiB

Open AccessArticle

Tetrandrine Induces Apoptosis of Human Nasopharyngeal Carcinoma NPC-TW 076 Cells through Reactive Oxygen Species Accompanied by an Endoplasmic Reticulum Stress Signaling Pathway

by Ya-Jing Lin¹, Shu-Fen Peng¹, Meng-Liang Lin², Chao-Lin Kuo³, Kung-Wen Lu⁴, Ching-Lung Liao⁴, Yi-Shih Ma^5,6, Fu-Shin Chueh⁷, Kuo-Ching Liu², Fu-Shun Yu^8,* and Jing-Gung Chung^1,9,*

¹ Department of Biological Science and Technology, China Medical University, Taichung 40402, Taiwan

² Department of Medical Laboratory Science and Biotechnology, China Medical University, Taichung 40402, Taiwan

³ Department of Chinese Pharmaceutical Sciences and Chinese Medicine Resources, China Medical University, Taichung 40402, Taiwan

⁴ College of Chinese Medicine, School of Post-Baccalaureate Chinese Medicine, China Medical University, Taichung 40402, Taiwan

⁵ Department of Chinese Medicine, E-Da Hospital, Kaohsiung 82445, Taiwan

⁶ School of Chinese Medicine for Post-Baccalaureate, I-Shou University, Kaohsiung 82445, Taiwan

⁷ Department of Health and Nutrition Biotechnology, Asia University, Wufeng, Taichung 41354, Taiwan

⁸ School of Dentistry, China Medical University, Taichung 40402, Taiwan

⁹ Department of Biotechnology, Asia University, Wufeng, Taichung 41354, Taiwan

Molecules 2016, 21(10), 1353; https://doi.org/10.3390/molecules21101353 - 12 Oct 2016

Cited by 27 | Viewed by 6538

Abstract

Nasopharyngeal carcinoma (NPC) is an epithelial malignancy of the head and neck and the incidence is higher in Southeast Asia. Tetrandrine (TET) is a bisbenzylisoquinoline alkaloid, a natural product, and exhibits biological activities including action against many human cancer cell lines. However, the [...] Read more.

Nasopharyngeal carcinoma (NPC) is an epithelial malignancy of the head and neck and the incidence is higher in Southeast Asia. Tetrandrine (TET) is a bisbenzylisoquinoline alkaloid, a natural product, and exhibits biological activities including action against many human cancer cell lines. However, the molecular mechanism of TET-induced cell apoptosis in human NPC cells is still unclear. In the present study, we investigated TET-induced apoptotic cell death and associated possible signal pathways on human nasopharyngeal carcinoma NPC-TW 076 cells in vitro. Phase contrast microscopy was used to examine cell morphology and DAPI staining was used to examine chromatin condensation. Flow cytometry assay was used to measure total viable cells, cell cycle and sub-G₁ phase distribution, reactive oxygen species (ROS), Ca²⁺, and mitochondria membrane potential (ΔΨ_m) in NPC-TW 076 cells. Results indicate that TET induced cell death through the cell morphological changes, caused G₀/G₁ phase arrest, increased ROS and Ca²⁺ production, and finally caused apoptotic cell death in NPC-TW 076 cells. There was no influence on the level of ΔΨ_m after TET treatment. Western blotting indicated that TET increased endoplasmic reticulum (ER) stress associated protein expression such as GADD153, GRP78, ATF-6α and ATF-6 βwhich indicated that TET induced cell death through ER stress. ER stress is a potential target in cancer treatment, so the ability of TET to induce ER stress response and to activate programming cell death in NPC-TW 076 cells make this molecule become a promising anticancer agent. Full article

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15 pages, 1002 KiB

Open AccessArticle

Effect of Exogenous Abscisic Acid and Methyl Jasmonate on Anthocyanin Composition, Fatty Acids, and Volatile Compounds of Cabernet Sauvignon (Vitis vinifera L.) Grape Berries

by Yan-Lun Ju¹, Min Liu¹, Hui Zhao¹, Jiang-Fei Meng¹ and Yu-Lin Fang^1,2,*

¹ College of Enology, Northwest A&F University, Yangling 712100, Shaanxi, China

² Shaanxi Engineering Research Center for Viti-Viniculture, Yangling 712100, Shaanxi, China

Molecules 2016, 21(10), 1354; https://doi.org/10.3390/molecules21101354 - 12 Oct 2016

Cited by 82 | Viewed by 6932

Abstract

The anthocyanin composition, fatty acids, and volatile aromas are important for Cabernet Sauvignon grape quality. This study evaluated the effect of exogenous abscisic acid (ABA) and methyl jasmonate (MeJA) on the anthocyanin composition, fatty acids, lipoxygenase activity, and the volatile compounds of Cabernet [...] Read more.

The anthocyanin composition, fatty acids, and volatile aromas are important for Cabernet Sauvignon grape quality. This study evaluated the effect of exogenous abscisic acid (ABA) and methyl jasmonate (MeJA) on the anthocyanin composition, fatty acids, lipoxygenase activity, and the volatile compounds of Cabernet Sauvignon grape berries. Exogenous ABA and MeJA improved the content of total anthocyanins (TAC) and individual anthocyanins. Lipoxygenase (LOX) activity also increased after treatment. Furthermore, 16 fatty acids were detected. The linoleic acid concentration gradually increased with ABA concentration. The fatty acid content decreased with increasing MeJA concentration and then increased again, with the exception of linoleic acid. After exogenous ABA and MeJA treatment, the C6 aroma content increased significantly. Interestingly, the exogenous ABA and MeJA treatments improved mainly the content of 1-hexanol, hexanal, and 2-heptanol. These results provide insight into the effect of plant hormones on wine grapes, which is useful for grape quality improvement. Full article

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15 pages, 2584 KiB

Open AccessCommunication

Exploiting 1,2,3-Triazolium Ionic Liquids for Synthesis of Tryptanthrin and Chemoselective Extraction of Copper(II) Ions and Histidine-Containing Peptides

by Hsin-Yi Li^†, Chien-Yuan Chen^†, Hui-Ting Cheng and Yen-Ho Chu^*

¹ Department of Chemistry and Biochemistry, National Chung Cheng University, Chiayi 62102, Taiwan

^† Both authors contributed equally to this work.

Molecules 2016, 21(10), 1355; https://doi.org/10.3390/molecules21101355 - 13 Oct 2016

Cited by 15 | Viewed by 8248

Abstract

Based on a common structural core of 4,5,6,7-tetrahydro[1,2,3]triazolo[1,5-a]pyridine, a number of bicyclic triazolium ionic liquids 1–3 were designed and successfully prepared. In our hands, this optimized synthesis of ionic liquids 1 and 2 requires no chromatographic separation. Also in [...] Read more.

Based on a common structural core of 4,5,6,7-tetrahydro[1,2,3]triazolo[1,5-a]pyridine, a number of bicyclic triazolium ionic liquids 1–3 were designed and successfully prepared. In our hands, this optimized synthesis of ionic liquids 1 and 2 requires no chromatographic separation. Also in this work, ionic liquids 1, 2 were shown to be efficient ionic solvents for fast synthesis of tryptanthrin natural product. Furthermore, a new affinity ionic liquid 3 was tailor-synthesized and displayed its effectiveness in chemoselective extraction of both Cu(II) ions and, for the first time, histidine-containing peptides. Full article

(This article belongs to the Special Issue Ionic Liquids and Deep Eutectic Solvents for Synthesis, Materials and Energy)

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17 pages, 3844 KiB

Open AccessReview

Mitoxantrone-Surfactant Interactions: A Physicochemical Overview

by Mirela Enache^1,*

, Ana Maria Toader¹

and Madalin Iancu Enache²

¹ Institute of Physical Chemistry Ilie Murgulescu, Romanian Academy, Splaiul Independentei 202, Bucharest 060021, Romania

² Institute of Biology Bucharest, Romanian Academy, Splaiul Independentei 296, Bucharest 060031, Romania

Molecules 2016, 21(10), 1356; https://doi.org/10.3390/molecules21101356 - 13 Oct 2016

Cited by 48 | Viewed by 9367

Abstract

Mitoxantrone is a synthetic anticancer drug used clinically in the treatment of different types of cancer. It was developed as a doxorubicin analogue in a program to find drugs with improved antitumor activity and decreased cardiotoxicity compared with the anthracyclines. As the cell [...] Read more.

Mitoxantrone is a synthetic anticancer drug used clinically in the treatment of different types of cancer. It was developed as a doxorubicin analogue in a program to find drugs with improved antitumor activity and decreased cardiotoxicity compared with the anthracyclines. As the cell membrane is the first barrier encountered by anticancer drugs before reaching the DNA sites inside the cells and as surfactant micelles are known as simple model systems for biological membranes, the drugs-surfactant interaction has been the subject of great research interest. Further, quantitative understanding of the interactions of drugs with biomimicking structures like surfactant micelles may provide helpful information for the control of physicochemical properties and bioactivities of encapsulated drugs in order to design better delivery systems with possible biomedical applications. The present review describes the physicochemical aspects of the interactions between the anticancer drug mitoxantrone and different surfactants. Mitoxantrone-micelle binding constants, partitions coefficient of the drug between aqueous and micellar phases and the corresponding Gibbs free energy for the above processes, and the probable location of drug molecules in the micelles are discussed. Full article

(This article belongs to the Collection Efficient Pharmaceutical and Chemical Approaches for Anticancer Therapy: Design, Preliminary Evaluations, and Further Developments)

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21 pages, 6503 KiB

Open AccessArticle

Small versus Large Iron Oxide Magnetic Nanoparticles: Hyperthermia and Cell Uptake Properties

by Cristian Iacovita¹, Adrian Florea²

, Roxana Dudric³, Emoke Pall⁴, Alin Iulian Moldovan⁵, Romulus Tetean³, Rares Stiufiuc^1,5,*

and Constantin Mihai Lucaciu^1,*

¹ Department of Pharmaceutical Physics-Biophysics, Faculty of Pharmacy, “Iuliu Hatieganu” University of Medicine and Pharmacy, Pasteur 6, 400349 Cluj-Napoca, Romania

² Department of Cell and Molecular Biology, Faculty of Medicine, ‘‘Iuliu Hatieganu’’ University of Medicine and Pharmacy, Pasteur 6, 400349 Cluj-Napoca, Romania

³ Faculty of Physics, “Babes Bolyai” University, Kogalniceanu 1, 400084 Cluj-Napoca, Romania

⁴ Department of Reproduction Obstetrics and Veterinary Gynecology, University of Agricultural Sciences and Veterinary Medicine, Manastur 3-5, 400372 Cluj-Napoca, Romania

⁵ Department of Bionanoscopy, MedFuture Research Center for Advance Medicine, “Iuliu Hatieganu” University of Medicine and Pharmacy, Pasteur 4-6, 400337 Cluj-Napoca, Romania

Molecules 2016, 21(10), 1357; https://doi.org/10.3390/molecules21101357 - 13 Oct 2016

Cited by 47 | Viewed by 7321

Abstract

Efficient use of magnetic hyperthermia in clinical cancer treatment requires biocompatible magnetic nanoparticles (MNPs), with improved heating capabilities. Small (~34 nm) and large (~270 nm) Fe₃O₄-MNPs were synthesized by means of a polyol method in polyethylene-glycol (PEG) and ethylene-glycol [...] Read more.

Efficient use of magnetic hyperthermia in clinical cancer treatment requires biocompatible magnetic nanoparticles (MNPs), with improved heating capabilities. Small (~34 nm) and large (~270 nm) Fe₃O₄-MNPs were synthesized by means of a polyol method in polyethylene-glycol (PEG) and ethylene-glycol (EG), respectively. They were systematically investigated by means of X-ray diffraction, transmission electron microscopy and vibration sample magnetometry. Hyperthermia measurements showed that Specific Absorption Rate (SAR) dependence on the external alternating magnetic field amplitude (up to 65 kA/m, 355 kHz) presented a sigmoidal shape, with remarkable SAR saturation values of ~1400 W/g_MNP for the small monocrystalline MNPs and only 400 W/g_MNP for the large polycrystalline MNPs, in water. SAR values were slightly reduced in cell culture media, but decreased one order of magnitude in highly viscous PEG1000. Toxicity assays performed on four cell lines revealed almost no toxicity for the small MNPs and a very small level of toxicity for the large MNPs, up to a concentration of 0.2 mg/mL. Cellular uptake experiments revealed that both MNPs penetrated the cells through endocytosis, in a time dependent manner and escaped the endosomes with a faster kinetics for large MNPs. Biodegradation of large MNPs inside cells involved an all-or-nothing mechanism. Full article

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23 pages, 4312 KiB

Open AccessReview

Methodology for the Construction of the Bicyclo[4.3.0]nonane Core

by Nicholas A. Eddy^* and Pranjali Ichalkaranje

Department of Chemistry, University of Connecticut, Storrs, CT 06269 USA

Molecules 2016, 21(10), 1358; https://doi.org/10.3390/molecules21101358 - 12 Oct 2016

Cited by 12 | Viewed by 11971

Abstract

The bicyclo[4.3.0]nonane scaffold, commonly known as a hydrindane, is a common structural motif found in many terpenoid structures and one that remains a challenge for synthetic chemists to elaborate with appropriate regio- and stereo-selectivity. Over the course of the study of terpene natural [...] Read more.

The bicyclo[4.3.0]nonane scaffold, commonly known as a hydrindane, is a common structural motif found in many terpenoid structures and one that remains a challenge for synthetic chemists to elaborate with appropriate regio- and stereo-selectivity. Over the course of the study of terpene natural products, the elaboration of the hydrindane structure has seen progress on the utilization of both old and newer methods to achieve the desired outcomes. This review seeks to serve as a general overview of these methods, and detail specific examples. Full article

(This article belongs to the Collection Triterpenes and Triterpenoids)

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10 pages, 413 KiB

Open AccessArticle

Chemical Compositions of Ligusticum chuanxiong Oil and Lemongrass Oil and Their Joint Action against Aphis citricola Van Der Goot (Hemiptera: Aphididae)

by Chao Zhang¹, Runqiang Liu¹, Jun He¹, Zhiqing Ma^1,2,*

and Xing Zhang^1,2

¹ Research and Development Center of Biorational Pesticide, Northwest Agriculture & Forestry University, Yangling 712100, Shaanxi, China

² Shaanxi Research Center of Biopesticide Engineering & Technology, Yangling 712100, Shaanxi, China

Molecules 2016, 21(10), 1359; https://doi.org/10.3390/molecules21101359 - 12 Oct 2016

Cited by 22 | Viewed by 8231

Abstract

In order to develop novel botanical insecticides, the joint action of Ligusticum chuanxiong oil (LCO) and lemongrass oil (LO) against Aphis citricola van der Goot was determined systematically indoors and outdoors. The chemical profiles of LCO and LO as determined by gas chromatography–mass [...] Read more.

In order to develop novel botanical insecticides, the joint action of Ligusticum chuanxiong oil (LCO) and lemongrass oil (LO) against Aphis citricola van der Goot was determined systematically indoors and outdoors. The chemical profiles of LCO and LO as determined by gas chromatography–mass spectrometry (GC-MS) analysis revealed that the main compounds from LCO were (Z)-ligustilide (44.58%) and senkyunolide A (26.92%), and that of LO were geranial (42.16%) and neral (32.58%), respectively. The mixture of LCO and LO showed significant synergy against A. citricola, with a common-toxicity coefficient (CTC) value of 221.46 at the optimal ratio of LCO to LO (4:1, w:w). Based on the results of solvents and emulsifiers screening, L. chuanxiong oil·Lemongrass oil 20% emulsifiable concentrate (20% LCO·LO EC) was developed, and its stability was confirmed with tests of cold and thermal storage. Field trials indicated that the insecticidal activity of the diluted 20% LCO·LO EC (1000 fold dilution) was comparable to conventional pesticide (20% imidacloprid EC) on A. citricola seven days after application. Thus, the mixture of LCO and LO has the potential to be further developed as a botanical pesticide. Full article

(This article belongs to the Collection Bioactive Compounds)

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13 pages, 5264 KiB

Open AccessArticle

Nujiangexathone A, a Novel Compound Derived from Garcinia nujiangensis, Induces Caspase-Dependent Apoptosis in Cervical Cancer through the ROS/JNK Pathway

by Li Zhang^1,2,†, Si-Yuan Kong^1,†

, Zhao-Qing Zheng¹, Xiao-Xiao Meng¹, Ji-Ling Feng¹, Hong-Sheng Tan¹

, Yuan-Zhi Lao¹, Lian-Bo Xiao^2,* and Hong-Xi Xu^1,2,*

¹ School of Pharmacy, Shanghai University of Traditional Chinese Medicine, No. 1200, Cailun Road, Shanghai 201203, China

² Institute of Arthritis Research, Shanghai Academy of Chinese Medical Sciences, Guanghua Integrative Medicine Hospital, No. 540, Xinhua Road, Shanghai 201203, China

^† These authors contributed equally to this work.

Molecules 2016, 21(10), 1360; https://doi.org/10.3390/molecules21101360 - 12 Oct 2016

Cited by 10 | Viewed by 6129

Abstract

Nujiangexathone A (NJXA), a novel compound derived from Garcinia nujiangensis, has been demonstrated to inhibit the proliferation of several human cancer cell lines. This study is the first to demonstrate the apoptosis inductive activities of NJXA and the possible underlying mechanisms. Our [...] Read more.

Nujiangexathone A (NJXA), a novel compound derived from Garcinia nujiangensis, has been demonstrated to inhibit the proliferation of several human cancer cell lines. This study is the first to demonstrate the apoptosis inductive activities of NJXA and the possible underlying mechanisms. Our results demonstrated that NJXA inhibited colony formation by HeLa and SiHa cells in a dose-dependent manner. An Annexin V-FITC/PI staining assay showed that NJXA strongly triggered apoptosis in a dose-dependent manner. Western blotting analyses showed that NJXA induced the caspase-dependent apoptosis of HeLa and SiHa cells by triggering a series of events, including changes in the levels of Bcl-2 family proteins, cytochrome c release, caspase-3 activation, and chromosome fragmentation. Furthermore, we demonstrated that NJXA induced cell apoptosis by activating the reactive oxygen species (ROS)-mediated JNK signaling pathway. Consistent with this finding, a ROS scavenger, N-acetyl-l-cysteine (NAC, 10 mM), hindered NJXA-induced apoptosis and attenuated the sensitivity of HeLa and SiHa cells to NJXA. In vivo results further confirmed that the tumor inhibitory effect of NJXA was partially through the induction of apoptosis. Taken together, our results demonstrated that NJXA induced the apoptosis of HeLa and SiHa cells through the ROS/JNK signaling pathway, indicating that NJXA could be important candidate for the clinical treatment of cervical cancer. Full article

(This article belongs to the Special Issue Selected papers from 2nd International Symposium on Phytochemicals in Medicine and Food (2-ISPMF, Fuzhou, 2017))

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10 pages, 887 KiB

Open AccessArticle

Three New Butenolides from the Fungus Aspergillus sp. CBS-P-2

by Xiao An^1,2,†, Yuehu Pei^1,2,†, Shaofei Chen^1,2, Shengge Li^1,2, Xiaolong Hu^1,2, Gang Chen^1,2, Bin Lin^2,3 and Haifeng Wang^1,2,*

¹ School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, China

² Key Laboratory of Structure-Based Drug Design and Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, China

³ Department of Medicinal Chemistry, School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang 110016, China

^† These authors contributed equally to this work.

Molecules 2016, 21(10), 1361; https://doi.org/10.3390/molecules21101361 - 13 Oct 2016

Cited by 9 | Viewed by 4795

Abstract

Three new butenolides aspernolides H–J (1–3) together with seven known ones (4–10) were isolated from the fungus Aspergillus sp. CBS-P-2. Their chemical structures were established on the basis of 1D- and 2D-NMR spectroscopic data, HR-ESI-MS [...] Read more.

Three new butenolides aspernolides H–J (1–3) together with seven known ones (4–10) were isolated from the fungus Aspergillus sp. CBS-P-2. Their chemical structures were established on the basis of 1D- and 2D-NMR spectroscopic data, HR-ESI-MS analysis, and their absolute configuration were determined by circular dichroism (CD) analysis. All the compounds were evaluated for the antioxidant effects by DPPH and ABTS methods, the antitumor activities against four human tumor cell lines (HL-60, ASPC1, HCT-116 and PC-3) and antimicrobial activities. Compounds 4–10 showed significant activity against DPPH (IC₅₀ = 15.9–34.3 μM) and compounds 1–10 exhibited significant ABTS free radical scavenging activity (IC₅₀ = 2.8–33.1 μM). Compounds 2, 5 and 11 showed potent cytotoxic activities against HL-60 cell lines with IC₅₀ values of 39.4, 13.2 and 16.3 μM, respectively. Compound 10 showed good antimicrobial activity against Staphylococcus aureus with minimum inhibitory concentration (MIC) of 21.3 μM. Full article

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14 pages, 2705 KiB

Open AccessReview

Chemical Components and Pharmacological Activities of Terpene Natural Products from the Genus Paeonia

by Dan-Dan Zhao^1,2,3

, Li-Li Jiang², Hong-Yi Li³, Peng-Fei Yan^1,* and Yan-Long Zhang^2,*

¹ Key Laboratory of Functional Inorganic Material Chemistry, Ministry of Education, School of Chemistry and Materials Science, Heilongjiang University, 74 Xue-Fu Road, Nan-Gang District, Harbin 150080, China

² Key Laboratory of Molecular Biology of Heilongjiang Province, College of Life Sciences, Heilongjiang University, Harbin 150080, China

³ Heilongjiang University Hospital, Harbin 150080, China

Molecules 2016, 21(10), 1362; https://doi.org/10.3390/molecules21101362 - 13 Oct 2016

Cited by 61 | Viewed by 10525

Abstract

Paeonia is the single genus of ca. 33 known species in the family Paeoniaceae, found in Asia, Europe and Western North America. Up to now, more than 180 compounds have been isolated from nine species of the genus Paeonia, including terpenes, [...] Read more.

Paeonia is the single genus of ca. 33 known species in the family Paeoniaceae, found in Asia, Europe and Western North America. Up to now, more than 180 compounds have been isolated from nine species of the genus Paeonia, including terpenes, phenols, flavonoids, essential oil and tannins. Terpenes, the most abundant naturally occurring compounds, which accounted for about 57% and occurred in almost every species, are responsible for the observed in vivo and in vitro biological activities. This paper aims to give a comprehensive overview of the recent phytochemical and pharmacological knowledge of the terpenes from Paeonia plants, and enlighten further drug discovery research. Full article

(This article belongs to the Collection Triterpenes and Triterpenoids)

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11 pages, 1729 KiB

Open AccessArticle

GC-MS Analysis of Membrane-Graded Fulvic Acid and Its Activity on Promoting Wheat Seed Germination

by Yi Qin^1,†, Hui Zhu^2,†, Mi Zhang¹, Huifen Zhang³, Cheng Xiang¹ and Baocai Li^1,*

¹ Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming 650500, China

² School of Chemistry and Chemical Engineering, Sichuan University of Arts and Science, Dazhou 635000, China

³ Food Security Research Institute of Yunnan Province, Kunming University of Science and Technology, Kunming 650500, China

^† These authors contributed equally to this work.

Molecules 2016, 21(10), 1363; https://doi.org/10.3390/molecules21101363 - 13 Oct 2016

Cited by 41 | Viewed by 7126

Abstract

The chemical composition of fulvic acid (FA) with a molecular weight below 500 (FA-500) was analyzed, and its activity on promoting the seed germination of wheat was studied in this paper. The FA-500 was obtained by membrane separation technology and qualitatively and quantitatively [...] Read more.

The chemical composition of fulvic acid (FA) with a molecular weight below 500 (FA-500) was analyzed, and its activity on promoting the seed germination of wheat was studied in this paper. The FA-500 was obtained by membrane separation technology and qualitatively and quantitatively analyzed by using gas chromatography-mass spectrometry combined with the retention index. Forty-seven constituents were identified, including structures with ester, acid and alcohol groups, which accounted for 95% of the total composition. The highest relative content of compounds was diethyl succinate and diethyl malonate, accounting for 29% and 17% of the total, respectively. Yannong 19 and Luyuan 301 wheat seeds were steeped with the FA-500 solution of different concentration respectively for two hours. Several markers were assessed: germination rate, coleoptile and radicle length, germination index, vitality index and the activity of α-amylase and (α+β) amylase. The results indicated that FA-500 had a significant effect on promoting seed germination within an appropriate concentration range. The best concentration was 0.5‰, and an inhibiting effect would appear with the increase of concentration. In the process of seed germination, FA-500 may affect the growth of the seed through influencing the amylase activity, which was related to respiration. Full article

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11 pages, 1788 KiB

Open AccessArticle

Solasonine, A Natural Glycoalkaloid Compound, Inhibits Gli-Mediated Transcriptional Activity

by Jun Yang, Wenjing Huang and Wenfu Tan^*

Department of Pharmacology, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai 201203, China

Molecules 2016, 21(10), 1364; https://doi.org/10.3390/molecules21101364 - 14 Oct 2016

Cited by 20 | Viewed by 5539

Abstract

The major obstacle limiting the efficacy of current Smoothened (Smo) inhibitors is the primary and acquired resistance mainly caused by Smo mutations and Gli amplification. In this context, developing Hh inhibitors targeting Gli, the final effector of this signaling pathway, may combat the [...] Read more.

The major obstacle limiting the efficacy of current Smoothened (Smo) inhibitors is the primary and acquired resistance mainly caused by Smo mutations and Gli amplification. In this context, developing Hh inhibitors targeting Gli, the final effector of this signaling pathway, may combat the resistance. In this study we found that solasonine, a natural glycoalkaloid compound, significantly inhibited the hedgehog (Hh) pathway activity. Meanwhile, solasonine may obviously inhibit the alkaline phosphatase (ALP) activity in C3H10T1/2 cells, concomitantly with reductions of the mRNA expression of Gli1 and Ptch1. However, we found that solasonine exhibited no effect on the transcriptional factors activities provoked by TNF-α and PGE2, thus suggesting its selectivity against Hh pathway activity. Furthermore, we identified that solasonine inhibited the Hh pathway activity by acting on its transcriptional factor Gli using a series of complementary data. We also observed that solasonine obviously inhibited the Gli-luciferase activity provoked by ectopic expression of Smo mutants which may cause the resistance to the current Smo inhibitors. Our study suggests that solasonine may significantly inhibit the Hh pathway activity by acting on Gli, therefore indicating the possibility to use solasonine as a lead compound to develop anticancer drugs for combating the resistance of current Smo inhibitors. Full article

(This article belongs to the Section Natural Products Chemistry)

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6 pages, 2192 KiB

Open AccessArticle

The Electroluminescence Mechanism of Solution-Processed TADF Emitter 4CzIPN Doped OLEDs Investigated by Transient Measurements

by Peng Wang^1,2, Suling Zhao^1,2,*, Zheng Xu^1,2, Bo Qiao^1,2, Zhijuan Long^1,2 and Qingyu Huang^1,2

¹ Institute of Optoelectronic Technology, Beijing Jiaotong University, Beijing 100044, China

² Key Laboratory of Luminescence and Optical Information, Ministry of Education, Beijing Jiaotong University, Beijing 100044, China

Molecules 2016, 21(10), 1365; https://doi.org/10.3390/molecules21101365 - 14 Oct 2016

Cited by 23 | Viewed by 10305

Abstract

High efficiency, solution-processed, organic light emitting devices (OLEDs), using a thermally-activated delayed fluorescent (TADF) emitter, 1,2,3,5-tetrakis(carbazol-9-yl)-4,6-dicyanobenzene (4CzIPN), are fabricated, and the transient electroluminescence (EL) decay of the device with a structure of [ITO/PEDOT: PSS/4CzIPN 5 wt % doped 4,40-N,N0-dicarbazolylbiphenyl(CBP)/bis-4,6-(3,5-di-4-pyridylphenyl)-2-methylpyrimidine (B4PyMPM)/lithium fluoride (LiF)/Al], is [...] Read more.

High efficiency, solution-processed, organic light emitting devices (OLEDs), using a thermally-activated delayed fluorescent (TADF) emitter, 1,2,3,5-tetrakis(carbazol-9-yl)-4,6-dicyanobenzene (4CzIPN), are fabricated, and the transient electroluminescence (EL) decay of the device with a structure of [ITO/PEDOT: PSS/4CzIPN 5 wt % doped 4,40-N,N0-dicarbazolylbiphenyl(CBP)/bis-4,6-(3,5-di-4-pyridylphenyl)-2-methylpyrimidine (B4PyMPM)/lithium fluoride (LiF)/Al], is systematically studied. The results shed light on the dominant operating mechanism in TADF-based OLEDs. Electroluminescence in the host–guest system is mainly produced from the 4CzIPN emitter, rather than the exciplex host materials. Full article

(This article belongs to the Special Issue Organic Light Emitting Diodes)

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19 pages, 2636 KiB

Open AccessArticle

Synthesis and In Vitro Cytotoxic Properties of Polycarbo-Substituted 4-(Arylamino)quinazolines

by Hugues Kamdem Paumo¹, Tshepiso Jan Makhafola² and Malose Jack Mphahlele^1,*

¹ Department of Chemistry, College of Science, Engineering and Technology, University of South Africa, Private Bag X06, Florida 1710, South Africa

² Department of Life and Consumer Sciences, College of Agriculture and Environmental Sciences, University of South Africa, Private Bag X06, Florida 1710, South Africa

Molecules 2016, 21(10), 1366; https://doi.org/10.3390/molecules21101366 - 14 Oct 2016

Cited by 9 | Viewed by 5705

Abstract

Herein, we describe the synthesis of novel unsymmetrical polycarbo-substituted 4-anilinoquinazolines derived from the 2-aryl-6-bromo-8-iodoquinazolines via one-pot three-step reaction sequences involving initial amination and subsequent double cross-coupling (bis-Suzuki, Sonogashira/Stille or Sonogashira/Suzuki-Miyaura) reactions with different cross coupling partners for the two carbon–carbon bond formation steps. [...] Read more.

Herein, we describe the synthesis of novel unsymmetrical polycarbo-substituted 4-anilinoquinazolines derived from the 2-aryl-6-bromo-8-iodoquinazolines via one-pot three-step reaction sequences involving initial amination and subsequent double cross-coupling (bis-Suzuki, Sonogashira/Stille or Sonogashira/Suzuki-Miyaura) reactions with different cross coupling partners for the two carbon–carbon bond formation steps. The 4-anilinoquinazolines were evaluated for potential cytotoxicity against three cancer cell lines, namely, human breast adenocarcinoma (MCF-7) cells, human cervical cancer (HeLa) and human lung cancer (A549) cells. The most active compounds, 2b, 2c, 3c, 4a, 4c and 5a, were found to be more selective against the MCF-7 and HeLa cell lines than the human lung carcinoma (A549) cells. We selected compounds 2c, 3c and 7a as representatives for further evaluation for potential to induce apoptosis and/or necrotic properties in the three cancer cell lines. Compound 2c induced apoptosis of MCF-7 cells through cell membrane alteration. Treatment of Hela and A549 cell lines with compounds 3c and 7a, respectively, led to caspase-3 activation in both cell lines. Compound 3c, on the other hand, caused more necrosis than apoptosis induction in the membrane alteration assay. Full article

(This article belongs to the Collection Heterocyclic Compounds)

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17 pages, 3443 KiB

Open AccessArticle

In Vitro Study on Anti-Hepatitis C Virus Activity of Spatholobus suberectus Dunn

by Shao-Ru Chen^1,†, An-Qi Wang^1,†, Li-Gen Lin¹

, Hong-Cong Qiu², Yi-Tao Wang^1,* and Ying Wang^1,*

¹ State Key Laboratory of Quality Research in Chinese Medicine and Institute of Chinese Medical Sciences, University of Macau, Avenida da Universidade, Taipa, Macao SAR 999078, China

² Guangxi Institute of Traditional Medical and Pharmaceutical Sciences and Guangxi Key Laboratory of Traditional Chinese Medicine Quality Standards, Nanning 530022, China

^† These authors contributed equally to this work.

Molecules 2016, 21(10), 1367; https://doi.org/10.3390/molecules21101367 - 15 Oct 2016

Cited by 31 | Viewed by 8603

Abstract

Hepatitis C virus (HCV) infects 200 million people worldwide, and 75% of HCV cases progress into chronic infections, which consequently cause cirrhosis and hepatocellular carcinoma. HCV infection is treated with currently considered standard drugs, including direct anti-viral agents (DAAs), alone or in combination [...] Read more.

Hepatitis C virus (HCV) infects 200 million people worldwide, and 75% of HCV cases progress into chronic infections, which consequently cause cirrhosis and hepatocellular carcinoma. HCV infection is treated with currently considered standard drugs, including direct anti-viral agents (DAAs), alone or in combination with peginterferon-α plus ribavirin. However, sustained viral responses vary in different cohorts, and high costs limit the broad use of DAAs. In this study, the ethanol and water extracts of 12 herbs from Lingnan in China were examined in terms of their inhibitory effect on HCV replication. Among the examined extracts, Spatholobus suberectus ethanol extracts suppressed HCV replication. By comparison, Extracts from Fructus lycii, Radix astragali (root), Rubus chingii Hu (fruit), Flos chrysanthemi Indici (flower), Cassia obtusifolia (seed), Lonicera japonica Thunb (flower), Forsythia suspense Thunb (fruit), Poria cocos (sclerotia), Carthamus tinctorius L. (flower), Crataegus pinnatifida Bge. (fruit), and Leonurus japonicas Houtt. (leaf) extracts failed to show a similar activity. Active S. suberectus fractions containing tannins as the major component also inhibited the in vitro translation of HCV RNA. The combination treatments of single compounds, such as epigallocatechin gallate and epicatechin gallate, were not as potent as crude S. suberectus fractions; therefore, crude S. suberectus extract may be a potential alternative treatment against HCV either alone or in combination with other agents. Full article

(This article belongs to the Special Issue Selected papers from 2nd International Symposium on Phytochemicals in Medicine and Food (2-ISPMF, Fuzhou, 2017))

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8 pages, 958 KiB

Open AccessArticle

The Determination of Food Dyes in Vitamins by RP-HPLC

by Monika Šuleková^*, Alexander Hudák and Miroslava Smrčová

Department of Chemistry, Biochemistry and Biophysics, Institute of Pharmaceutical Chemistry, The University of Veterinary Medicine and Pharmacy in Košice, Košice 04181, Slovakia

Molecules 2016, 21(10), 1368; https://doi.org/10.3390/molecules21101368 - 17 Oct 2016

Cited by 30 | Viewed by 11716

Abstract

Reversed-phase high performance liquid chromatography (RP-HPLC) for the determination of five synthetic food dyes (Quinoline Yellow E104, Sunset Yellow E110, Ponceau 4R E124, Tartrazine E102 and Carmine E120) in vitamins was used. The dyes were analyzed within 10 min using a column with [...] Read more.

Reversed-phase high performance liquid chromatography (RP-HPLC) for the determination of five synthetic food dyes (Quinoline Yellow E104, Sunset Yellow E110, Ponceau 4R E124, Tartrazine E102 and Carmine E120) in vitamins was used. The dyes were analyzed within 10 min using a column with stationary phase C 18 (250 mm × 4.6 mm, 5 μm) at 40 °C with isocratic elution, and the mobile phase contained acetonitrile and a mixture of CH₃COONa:CH₃OH (85:15, v/v) in a ratio of 10:90 (v/v) for yellow-colored capsules and 20:80 (v/v) for red-colored capsules, respectively. A diode-array detector was used to monitor the dyes between 190 and 800 nm. It was established that the analyzed samples contained synthetic dyes in a concentration range from 79.5 ± 0.01 μg/capsule of Ponceau 4R, E124 to 524 ± 0.01 μg/capsule of Tartrazine, E102. The obtained results were compared with existing acceptable daily intakes (ADIs) for individual dyes. This paper provides information about the content of dyes in samples of vitamins. This information is not generally available to consumers. Full article

(This article belongs to the Special Issue Selected Papers from the 8th Central European Conference ‘Chemistry towards Biology’ (CTB-2016))

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13 pages, 2149 KiB

Open AccessArticle

Coumarin Antifungal Lead Compounds from Millettia thonningii and Their Predicted Mechanism of Action

by Daniel M. Ayine-Tora^1,2, Robert Kingsford-Adaboh², William A. Asomaning², Jerry J.E.K. Harrison², Felix C. Mills-Robertson³, Yahaya Bukari⁴, Patrick O. Sakyi², Sylvester Kaminta⁵

and Jóhannes Reynisson^1,*

¹ School of Chemical Sciences, University of Auckland, 23 Symonds Street, 1142 Auckland, New Zealand

² Department of Chemistry, University of Ghana, LG 56, Legon-Accra, Ghana

³ Department of Biochemistry and Biotechnology, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana

⁴ Botany Department, University of Ghana, LG 55, Legon-Accra, Ghana

⁵ Centre for Plant Medicine Research, 73, Mampong-Akuapem, Ghana

Molecules 2016, 21(10), 1369; https://doi.org/10.3390/molecules21101369 - 15 Oct 2016

Cited by 26 | Viewed by 7314

Abstract

Fungal pathogens continue to pose challenges to humans and plants despite efforts to control them. Two coumarins, robustic acid and thonningine-C isolated from Millettia thonningii, show promising activity against the fungus Candida albicans with minimum fungicidal concentration of 1.0 and 0.5 mg/mL, [...] Read more.

Fungal pathogens continue to pose challenges to humans and plants despite efforts to control them. Two coumarins, robustic acid and thonningine-C isolated from Millettia thonningii, show promising activity against the fungus Candida albicans with minimum fungicidal concentration of 1.0 and 0.5 mg/mL, respectively. Molecular modelling against the putative bio-molecular target, lanosterol 14α-demethylase (CYP51), revealed a plausible binding mode for the active compounds, in which the hydroxyl group binds with a methionine backbone carboxylic group blocking access to the iron catalytic site. This binding disrupts the synthesis of several important sterols for the survival of fungi. Full article

(This article belongs to the Section Natural Products Chemistry)

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19 pages, 1250 KiB

Open AccessReview

Enzyme Engineering for In Situ Immobilization

by Fabian B. H. Rehm, Shuxiong Chen and Bernd H. A. Rehm^*

Institute of Fundamental Sciences, Massey University, Private Bag 11222, Palmerston North 4442, New Zealand

Molecules 2016, 21(10), 1370; https://doi.org/10.3390/molecules21101370 - 14 Oct 2016

Cited by 97 | Viewed by 13939

Abstract

Enzymes are used as biocatalysts in a vast range of industrial applications. Immobilization of enzymes to solid supports or their self-assembly into insoluble particles enhances their applicability by strongly improving properties such as stability in changing environments, re-usability and applicability in continuous biocatalytic [...] Read more.

Enzymes are used as biocatalysts in a vast range of industrial applications. Immobilization of enzymes to solid supports or their self-assembly into insoluble particles enhances their applicability by strongly improving properties such as stability in changing environments, re-usability and applicability in continuous biocatalytic processes. The possibility of co-immobilizing various functionally related enzymes involved in multistep synthesis, conversion or degradation reactions enables the design of multifunctional biocatalyst with enhanced performance compared to their soluble counterparts. This review provides a brief overview of up-to-date in vitro immobilization strategies while focusing on recent advances in enzyme engineering towards in situ self-assembly into insoluble particles. In situ self-assembly approaches include the bioengineering of bacteria to abundantly form enzymatically active inclusion bodies such as enzyme inclusions or enzyme-coated polyhydroxyalkanoate granules. These one-step production strategies for immobilized enzymes avoid prefabrication of the carrier as well as chemical cross-linking or attachment to a support material while the controlled oriented display strongly enhances the fraction of accessible catalytic sites and hence functional enzymes. Full article

(This article belongs to the Special Issue Enzyme Immobilization 2016)

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21 pages, 7661 KiB

Open AccessReview

Synthesis, Properties and Stereochemistry of 2-Halo-1,2λ⁵-oxaphosphetanes

by Anastasy O. Kolodiazhna and Oleg I. Kolodiazhnyi^*

Institute of Bioorganic Chemistry and Petrochemistry, National Academy of Sciences of Ukraine, 1, Murmanska Street, Kiev 02094, Ukraine

Molecules 2016, 21(10), 1371; https://doi.org/10.3390/molecules21101371 - 17 Oct 2016

Cited by 6 | Viewed by 7344

Abstract

Results of research into four-membered 2-halo-1,2λ⁵-oxaphosphetane phosphorus(V)-heterocycles are presented. The preparation of 2-halo-1,2λ⁵-oxaphosphetanes by reaction of P-haloylides with carbonyl compounds is described. The mechanism of asynchronous [2+2]-сycloaddition of ylides to aldehydes was proposed on the base of low-temperature [...] Read more.

Results of research into four-membered 2-halo-1,2λ⁵-oxaphosphetane phosphorus(V)-heterocycles are presented. The preparation of 2-halo-1,2λ⁵-oxaphosphetanes by reaction of P-haloylides with carbonyl compounds is described. The mechanism of asynchronous [2+2]-сycloaddition of ylides to aldehydes was proposed on the base of low-temperature NMR investigations. 2-Halo-1,2λ⁵-oxaphosphetanes were isolated as individual compounds and their structures were confirmed by ¹Н-, ¹³C-, ¹⁹F- and ³¹Р-NMR spectra. These compounds are convenient reagents for preparing of various organic and organophosphorus compounds hardly available by other methods. Chemical and physical properties of the 2-halo-1,2λ⁵-oxaphosphetanes are reviewed. The 2-chloro-1,2λ⁵-oxaphosphetanes, rearrange with formation of 2-chloroalkyl-phosphonates or convert into trans-phosphorylated alkenes depending on the substituents at the α-carbon atom. Prospective synthetic applications of 2-halo-1,2λ⁵-oxaphosphetanes are analyzed. The 2-halo-1,2λ⁵-oxaphosphetanes may be easily converted to various alkenylphosphonates: allyl- or vinylphosphonates, phosphorus ketenes, thioketenes, ketenimines. Full article

(This article belongs to the Special Issue Recent Advances in Organophosphorus Chemistry)

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12 pages, 240 KiB

Open AccessArticle

Development of Mushroom-Based Cosmeceutical Formulations with Anti-Inflammatory, Anti-Tyrosinase, Antioxidant, and Antibacterial Properties

by Oludemi Taofiq^1,2,3, Sandrina A. Heleno^1,3, Ricardo C. Calhelha¹, Maria José Alves⁴, Lillian Barros¹, Maria Filomena Barreiro³

, Ana M. González-Paramás²

and Isabel C. F. R. Ferreira^1,*

¹ Mountain Research Centre (CIMO), ESA, Polytechnic Institute of Bragança, Campus de Santa Apolónia, 1172, 5300-253 Bragança, Portugal

² GIP-USAL, Unidad de Nutrición y Bromatología, Faculty of Pharmacy, University of Salamanca, Campus Miguel de Unamuno, 37007 Salamanca, Spain

³ Laboratory of Separation and Reaction Engineering (LSRE), Associate Laboratory LSRE/LCM, Polytechnic Institute of Bragança, Campus de Santa Apolónia, 1134, 5301-857 Bragança, Portugal

⁴ School of Health, Polytechnic Institute of Bragança, Av. D. Afonso V, 5300-121 Bragança, Portugal

Molecules 2016, 21(10), 1372; https://doi.org/10.3390/molecules21101372 - 14 Oct 2016

Cited by 95 | Viewed by 12601

Abstract

The cosmetic industry is in a constant search for natural compounds or extracts with relevant bioactive properties, which became valuable ingredients to design cosmeceutical formulations. Mushrooms have been markedly studied in terms of nutritional value and medicinal properties. However, there is still slow [...] Read more.

The cosmetic industry is in a constant search for natural compounds or extracts with relevant bioactive properties, which became valuable ingredients to design cosmeceutical formulations. Mushrooms have been markedly studied in terms of nutritional value and medicinal properties. However, there is still slow progress in the biotechnological application of mushroom extracts in cosmetic formulations, either as antioxidants, anti-aging, antimicrobial, and anti-inflammatory agents or as hyperpigmentation correctors. In the present work, the cosmeceutical potential of ethanolic extracts prepared from Agaricus bisporus, Pleurotus ostreatus, and Lentinula edodes was analyzed in terms of anti-inflammatory, anti-tyrosinase, antioxidant, and antibacterial activities. The extracts were characterized in terms of phenolic acids and ergosterol composition, and further incorporated in a base cosmetic cream to achieve the same bioactive purposes. From the results obtained, the final cosmeceutical formulations presented 85%–100% of the phenolic acids and ergosterol levels found in the mushroom extracts, suggesting that there was no significant loss of bioactive compounds. The final cosmeceutical formulation also displayed all the ascribed bioactivities and as such, mushrooms can further be exploited as natural cosmeceutical ingredients. Full article

(This article belongs to the Collection Bioactive Compounds)

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14 pages, 5455 KiB

Open AccessArticle

Comparative Studies of Interactions between Fluorodihydroquinazolin Derivatives and Human Serum Albumin with Fluorescence Spectroscopy

by Yi Wang^1,2

, Meiqing Zhu¹

, Feng Liu², Xiangwei Wu¹, Dandan Pan¹, Jia Liu^1,3, Shisuo Fan¹, Zhen Wang¹, Jun Tang¹, Risong Na^1,3, Qing X. Li⁴

, Rimao Hua^1,* and Shangzhong Liu^2,*

¹ Department of Science of Pesticides, School of Resources and Environment, Anhui Agricultural University, No. 130 Changjiang West Road, Hefei 230036, China

² Department of Applied Chemistry, China Agricultural University, No. 2 Yuanmingyuan West Road, Beijing 100193, China

³ Collaborative Innovation Center of Henan Grain Crops, National Key Laboratory of Wheat and Maize Crop Science, College of Plant Protection, Henan Agricultural University, Wenhua Road No. 95, Zhengzhou 450002, China

⁴ Department of Molecular Biosciences and Bioengineering, University of Hawaii, 1955 East-West Road, Honolulu, HI 96822, USA

Molecules 2016, 21(10), 1373; https://doi.org/10.3390/molecules21101373 - 14 Oct 2016

Cited by 19 | Viewed by 5573

Abstract

In the present study, 3-(fluorobenzylideneamino)-6-chloro-1-(3,3-dimethylbutanoyl)-phenyl-2,3-dihydroquinazolin-4(1H)-one (FDQL) derivatives have been designed and synthesized to study the interaction between fluorine substituted dihydroquinazoline derivatives with human serum albumin (HSA) using fluorescence, circular dichroism and Fourier transform infrared spectroscopy. The results indicated that the FDQL [...] Read more.

In the present study, 3-(fluorobenzylideneamino)-6-chloro-1-(3,3-dimethylbutanoyl)-phenyl-2,3-dihydroquinazolin-4(1H)-one (FDQL) derivatives have been designed and synthesized to study the interaction between fluorine substituted dihydroquinazoline derivatives with human serum albumin (HSA) using fluorescence, circular dichroism and Fourier transform infrared spectroscopy. The results indicated that the FDQL could bind to HSA, induce conformation and the secondary structure changes of HSA, and quench the intrinsic fluorescence of HSA through a static quenching mechanism. The thermodynamic parameters, ΔH, ΔS, and ΔG, calculated at different temperatures, revealed that the binding was through spontaneous and hydrophobic forces and thus played major roles in the association. Based on the number of binding sites, it was considered that one molecule of FDQL could bind to a single site of HSA. Site marker competition experiments indicated that the reactive site of HSA to FDQL mainly located in site II (subdomain IIIA). The substitution by fluorine in the benzene ring could increase the interactions between FDQL and HSA to some extent in the proper temperature range through hydrophobic effect, and the substitution at meta-position enhanced the affinity greater than that at para- and ortho-positions. Full article

(This article belongs to the Special Issue Fluorine Chemistry 2016)

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19 pages, 1357 KiB

Open AccessReview

An Overview of Plant Phenolic Compounds and Their Importance in Human Nutrition and Management of Type 2 Diabetes

by Derong Lin^1,*,†, Mengshi Xiao^1,†, Jingjing Zhao^1,†, Zhuohao Li^1,†, Baoshan Xing², Xindan Li^1,†, Maozhu Kong^1,†, Liangyu Li^1,†, Qing Zhang¹, Yaowen Liu¹, Hong Chen¹, Wen Qin¹, Hejun Wu¹ and Saiyan Chen¹

¹ College of Food Science, Sichuan Agricultural University, No. 46, Xinkang Road, Ya’an 625014, Sichuan, China

² Stockbridge School of Agriculture, University of Massachusetts, Amherst, MA 01003, USA

^† These authors contributed equally to this work.

Molecules 2016, 21(10), 1374; https://doi.org/10.3390/molecules21101374 - 15 Oct 2016

Cited by 870 | Viewed by 39412

Abstract

In this paper, the biosynthesis process of phenolic compounds in plants is summarized, which includes the shikimate, pentose phosphate and phenylpropanoid pathways. Plant phenolic compounds can act as antioxidants, structural polymers (lignin), attractants (flavonoids and carotenoids), UV screens (flavonoids), signal compounds (salicylic acid [...] Read more.

In this paper, the biosynthesis process of phenolic compounds in plants is summarized, which includes the shikimate, pentose phosphate and phenylpropanoid pathways. Plant phenolic compounds can act as antioxidants, structural polymers (lignin), attractants (flavonoids and carotenoids), UV screens (flavonoids), signal compounds (salicylic acid and flavonoids) and defense response chemicals (tannins and phytoalexins). From a human physiological standpoint, phenolic compounds are vital in defense responses, such as anti-aging, anti-inflammatory, antioxidant and anti-proliferative activities. Therefore, it is beneficial to eat such plant foods that have a high antioxidant compound content, which will cut down the incidence of certain chronic diseases, for instance diabetes, cancers and cardiovascular diseases, through the management of oxidative stress. Furthermore, berries and other fruits with low-amylase and high-glucosidase inhibitory activities could be regarded as candidate food items in the control of the early stages of hyperglycemia associated with type 2 diabetes. Full article

(This article belongs to the Special Issue Selected papers from 2nd International Symposium on Phytochemicals in Medicine and Food (2-ISPMF, Fuzhou, 2017))

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26 pages, 6545 KiB

Open AccessReview

Novel Natural Product- and Privileged Scaffold-Based Tubulin Inhibitors Targeting the Colchicine Binding Site

by Mengqi Dong¹, Fang Liu¹, Hongyu Zhou², Shumei Zhai^1,* and Bing Yan^2,*

¹ School of Chemistry and Chemical Engineering, Shandong University, Jinan 250100, China

² School of Environment, Guangzhou Key Laboratory of Environmental Exposure and Health and Guangdong Key Laboratory of Environmental Pollution and Health, Jinan University, Guangzhou 510632, China

Molecules 2016, 21(10), 1375; https://doi.org/10.3390/molecules21101375 - 15 Oct 2016

Cited by 69 | Viewed by 12531

Abstract

Tubulin inhibitors are effective anticancer agents, however, there are many limitations to the use of available tubulin inhibitors in the clinic, such as multidrug resistance, severe side-effects, and generally poor bioavailability. Thus, there is a constant need to search for novel tubulin inhibitors [...] Read more.

Tubulin inhibitors are effective anticancer agents, however, there are many limitations to the use of available tubulin inhibitors in the clinic, such as multidrug resistance, severe side-effects, and generally poor bioavailability. Thus, there is a constant need to search for novel tubulin inhibitors that can overcome these limitations. Natural product and privileged structures targeting tubulin have promoted the discovery and optimization of tubulin inhibitors. This review will focus on novel tubulin inhibitors derived from natural products and privileged structures targeting the colchicine binding site on tubulin. Full article

(This article belongs to the Special Issue Tubulin Inhibitors)

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10 pages, 3796 KiB

Open AccessArticle

Reactions of an Isolable Dialkylsilylene with Aroyl Chlorides. A New Route to Aroylsilanes

by Xu-Qiong Xiao, Xupeng Liu, Qiong Lu, Zhifang Li^*, Guoqiao Lai and Mitsuo Kira^*

Key Laboratory of Organosilicon Chemistry and Material Technology of Ministry of Education, Hangzhou Normal University, Hangzhou 311121, China

Molecules 2016, 21(10), 1376; https://doi.org/10.3390/molecules21101376 - 15 Oct 2016

Cited by 8 | Viewed by 5070

Abstract

The reactions of isolable dialkylsilylene 1 with aromatic acyl chlorides afforded aroylsilanes 3a–3c exclusively. Aroylsilanes 3a–3c were characterized by ¹H-, ¹³C-, and ²⁹Si-NMR spectroscopy, high-resolution mass spectrometry (HRMS), and single-crystal molecular structure analysis. The reaction mechanisms [...] Read more.

The reactions of isolable dialkylsilylene 1 with aromatic acyl chlorides afforded aroylsilanes 3a–3c exclusively. Aroylsilanes 3a–3c were characterized by ¹H-, ¹³C-, and ²⁹Si-NMR spectroscopy, high-resolution mass spectrometry (HRMS), and single-crystal molecular structure analysis. The reaction mechanisms are discussed in comparison with related reaction of 1 with chloroalkanes and chlorosilanes. Full article

(This article belongs to the Special Issue Advances in Silicon Chemistry)

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13 pages, 5083 KiB

Open AccessArticle

A Novel Tetrahydrocannabinol Electrochemical Nano Immunosensor Based on Horseradish Peroxidase and Double-Layer Gold Nanoparticles

by Dingqiang Lu^1,2,3,4, Fuping Lu^1,2 and Guangchang Pang^1,2,3,4,*

¹ College of Biotechnology, Tianjin University of Science &Technology, Tianjin 300457, China

² Key Laboratory of Industrial Fermentation Microbiology, Ministry of Education, Tianjin 300457, China

³ College of Biotechnology & Food Science, Tianjin University of Commerce, Tianjin 300314, China

⁴ Tianjin Key Laboratory of Food Biotechnology, Tianjin 300314, China

Molecules 2016, 21(10), 1377; https://doi.org/10.3390/molecules21101377 - 17 Oct 2016

Cited by 25 | Viewed by 7079

Abstract

In the current study, a novel double-layer gold nanoparticles-electrochemical immunosensor electrode immobilized with tetrahydrocannabinol (THC) antibody derived from Balb/c mice was developed. To increase the fixed quantity of antibodies and electrochemical signals, an electrochemical biosensing signal amplification system was utilized with gold nanoparticles-thionine-chitosan [...] Read more.

In the current study, a novel double-layer gold nanoparticles-electrochemical immunosensor electrode immobilized with tetrahydrocannabinol (THC) antibody derived from Balb/c mice was developed. To increase the fixed quantity of antibodies and electrochemical signals, an electrochemical biosensing signal amplification system was utilized with gold nanoparticles-thionine-chitosan absorbing horseradish peroxidase (HRP). In addition, a transmission electron microscope (TEM) was used to characterize the nanogold solution. To evaluate the quality of the immunosensor, the amperometric I-t curve method was applied to determine the THC in PBS. The results showed that the response current had a good linear correlation with the THC concentration range from 0.01~10³ ng/mL with a correlation coefficient of 0.9986. The lowest detection limit for THC was 3.3 pg/mL (S/N = 3). Moreover, it was validated with high sensitivity and reproducibility. Apparently, the immunosensor may be a very useful tool for monitoring the THC. Full article

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12 pages, 1789 KiB

Open AccessArticle

The Inhibition Effect of Cell DNA Oxidative Damage and LDL Oxidation by Bovine Colostrums

by Chih-Wei Chen¹

, Chi-Yue Chang¹ and Shu-Hua Chiang^2,*

¹ Department of Health Food, Chung Chou University of Science and Technology, Changhua 51591, Taiwan

² Department of Health and Creative Vegetarian Science, Fo Guang University, No. 160, Linwei Rd., Jiaosi, Yilan County 26247, Taiwan

Molecules 2016, 21(10), 1378; https://doi.org/10.3390/molecules21101378 - 21 Oct 2016

Cited by 12 | Viewed by 4460

Abstract

In the present study, we investigated the effect of bovine colostrums on inhibition of DNA oxidative damage and low density lipoprotein (LDL) oxidation in vitro. Results showed that whey and skimmed milk exhibited not only higher inhibitory activities of oxidative damage of deoxyribose [...] Read more.

In the present study, we investigated the effect of bovine colostrums on inhibition of DNA oxidative damage and low density lipoprotein (LDL) oxidation in vitro. Results showed that whey and skimmed milk exhibited not only higher inhibitory activities of oxidative damage of deoxyribose but also an inhibitory effect on the breakdown of supercoiled DNA into open circular DNA and linear DNA. The quantities of 8-OH-2′-dG formed under whey, caseins and skimmed milk treatment were 0.24, 0.24 and 1.24 μg/mL, respectively. The quantity of malondialdehyde formed through LDL oxidation induced by copprous ion was significantly decreased as colostrums protein solutions were added, in which whey and caseins led to a more significant decrease than skimmed milk. The formation of conjugated dienes could be inhibited by treatment with colostrums protein solutions. Whey exhibited the longest lag time of conjugated dienes formation among the colostrums proteins. The lag time of the whey was 2.33 times that of the control. From the results of foregoing, the bovine colostrums protein has potential value in the inhibition of DNA oxidation damage and LDL oxidation. Full article

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10 pages, 3148 KiB

Open AccessArticle

Transcriptome Profile Reveals that Pu-Erh Tea Represses the Expression of Vitellogenin Family to Reduce Fat Accumulation in Caenorhabditis elegans

by Ru-Yue Xiao¹, Junjun Hao², Yi-Hong Ding³, Yan-Yun Che⁴, Xiao-Ju Zou^5,* and Bin Liang^3,*

¹ Pharmaceutical College, Heilongjiang University of Chinese Medicine, #24Heping Road, Harbin 150040, China

² State Key Laboratory of Genetic Resources and Evolutionary & Functional Genomics, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China

³ Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences & Yunnan province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China

⁴ Pharmaceutical College, Yunnan University of Traditional Chinese Medicine, Kunming 650500, China

⁵ Department of Life Science and Biotechnology, Key Laboratory of Special Biological Resource Development and Utilization of University in Yunnan Province, Kunming University, Kunming 650214, China

Molecules 2016, 21(10), 1379; https://doi.org/10.3390/molecules21101379 - 17 Oct 2016

Cited by 4 | Viewed by 7402

Abstract

Due to misbalanced energy surplus and expenditure, obesity has become a common chronic disorder that is highly associated with many metabolic diseases. Pu-erh tea, a traditional Chinese beverage, has been believed to have numerous health benefits, such as anti-obesity. However, the underlying mechanisms [...] Read more.

Due to misbalanced energy surplus and expenditure, obesity has become a common chronic disorder that is highly associated with many metabolic diseases. Pu-erh tea, a traditional Chinese beverage, has been believed to have numerous health benefits, such as anti-obesity. However, the underlying mechanisms of its anti-obesity effect are yet to be understood. Here, we take the advantages of transcriptional profile by RNA sequencing (RNA-Seq) to view the global gene expression of Pu-erh tea. The model organism Caenorhabditis elegans was treated with different concentrations of Pu-erh tea water extract (PTE, 0 g/mL, 0.025 g/mL, and 0.05 g/mL). Compared with the control, PTE indeed decreases lipid droplets size and fat accumulation. The high-throughput RNA-Sequence technique detected 18073 and 18105 genes expressed in 0.025 g/mL and 0.05 g/mL PTE treated groups, respectively. Interestingly, the expression of the vitellogenin family (vit-1, vit-2, vit-3, vit-4 and vit-5) was significantly decreased by PTE, which was validated by qPCR analysis. Furthermore, vit-1(ok2616), vit-3(ok2348) and vit-5(ok3239) mutants are insensitive to PTE triggered fat reduction. In conclusion, our transcriptional profile by RNA-Sequence suggests that Pu-erh tea lowers the fat accumulation primarily through repression of the expression of vit(vitellogenin) family, in addition to our previously reported (sterol regulatory element binding protein) SREBP-SCD (stearoyl-CoA desaturase) axis. Full article

(This article belongs to the Special Issue Natural Products in Anti-Obesity Therapy)

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14 pages, 1997 KiB

Open AccessArticle

Simultaneous Saccharification and Fermentation of Sugar Beet Pulp with Mixed Bacterial Cultures for Lactic Acid and Propylene Glycol Production

by Joanna Berlowska^1,*

, Weronika Cieciura¹, Sebastian Borowski¹, Marta Dudkiewicz¹, Michal Binczarski², Izabela Witonska², Anna Otlewska¹ and Dorota Kregiel¹

¹ Institute of Fermentation Technology and Microbiology, Lodz University of Technology, Wolczanska 171/173, 90-924 Lodz, Poland

² Institute of General and Ecological Chemistry, Lodz University of Technology, Zeromskiego 116, 90-924 Lodz, Poland

Molecules 2016, 21(10), 1380; https://doi.org/10.3390/molecules21101380 - 17 Oct 2016

Cited by 37 | Viewed by 8799

Abstract

Research into fermentative production of lactic acid from agricultural by-products has recently concentrated on the direct conversion of biomass, whereby pure sugars are replaced with inexpensive feedstock in the process of lactic acid production. In our studies, for the first time, the source [...] Read more.

Research into fermentative production of lactic acid from agricultural by-products has recently concentrated on the direct conversion of biomass, whereby pure sugars are replaced with inexpensive feedstock in the process of lactic acid production. In our studies, for the first time, the source of carbon used is sugar beet pulp, generated as a by-product of industrial sugar production. In this paper, we focus on the simultaneous saccharification of lignocellulosic biomass and fermentation of lactic acid, using mixed cultures with complementary assimilation profiles. Lactic acid is one of the primary platform chemicals, and can be used to synthesize a wide variety of useful products, including green propylene glycol. A series of controlled batch fermentations was conducted under various conditions, including pretreatment with enzymatic hydrolysis. Inoculation was performed in two sequential stages, to avoid carbon catabolite repression. Biologically-synthesized lactic acid was catalytically reduced to propylene glycol over 5% Ru/C. The highest lactic acid yield was obtained with mixed cultures. The yield of propylene glycol from the biological lactic acid was similar to that obtained with a water solution of pure lactic acid. Our results show that simultaneous saccharification and fermentation enables generation of lactic acid, suitable for further chemical transformations, from agricultural residues. Full article

(This article belongs to the Special Issue Chemicals from Biomass)

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27 pages, 1004 KiB

Open AccessConference Report

The Eighth Central European Conference “Chemistry towards Biology”: Snapshot

by András Perczel^1,*, Atanas G. Atanasov^2,3,*

, Vladimír Sklenář⁴, Jiří Nováček⁴, Veronika Papoušková⁴, Pavel Kadeřávek⁴, Lukáš Žídek⁴, Henryk Kozłowski⁵, Joanna Wątły⁵

, Aleksandra Hecel⁵, Paulina Kołkowska⁵, Jaroslav Koča^4,6, Radka Svobodová-Vařeková^4,6, Lukáš Pravda^4,6

, David Sehnal^4,6, Vladimír Horský^4,6, Stanislav Geidl^4,6, Ricardo D. Enriz^7,8, Pavel Matějka⁹, Adéla Jeništová⁹, Marcela Dendisová⁹, Alžběta Kokaislová⁹, Volkmar Weissig¹⁰, Mark Olsen¹⁰, Aidan Coffey¹¹

, Jude Ajuebor¹¹, Ruth Keary¹¹, Marta Sanz-Gaitero¹², Mark J. Van Raaij¹²

, Olivia McAuliffe¹³, Birgit Waltenberger¹⁴, Andrei Mocan¹⁵, Karel Šmejkal¹⁶, Elke H. Heiss², Marc Diederich¹⁷

, Robert Musioł¹⁸, Janez Košmrlj¹⁹, Jarosław Polański¹⁸ and Josef Jampílek^20,*

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¹ Laboratory of Structural Chemistry and Biology and MTA-ELTE Protein Modeling Research Group at the Institute of Chemistry, Eötvös Loránd University, 1518, 112, PO Box 32, H-1053 Budapest, Hungary

² Department of Pharmacognosy, Faculty of Life Sciences, University of Vienna, Althanstrasse 14, 1090 Vienna, Austria

³ Institute of Genetics and Animal Breeding of the Polish Academy of Sciences, ul. Postepu 36A, 05552 Jastrzebiec, Poland

⁴ Central European Institute of Technology, Masaryk University, Kamenice 5, 62500 Brno, Czech Republic

⁵ Department of Biological Chemistry, Faculty of Chemistry, University of Wroclaw, F. Joliot-Curie 14, 50-383 Wroclaw, Poland

⁶ National Centre for Biomolecular Research, Faculty of Science, Masaryk University, Kamenice 5, 62500 Brno, Czech Republic

⁷ Facultad de Química, Bioquímica y Farmacia, Universidad Nacional de San Luis, Chacabuco 917, 5700 San Luis, Argentina

⁸ Instituto Multidisciplinario de Investigaciones Biológicas de San Luis, Ejercito de Los Andes 950, 5700 San Luis, Argentina

⁹ Department of Physical Chemistry, Faculty of Chemical Engineering, University of Chemistry and Technology, Technická 5, 16628 Prague 6, Czech republic

¹⁰ Department of Medical Chemistry, College of Pharmacy Glendale, Midwestern University, 19555 N. 59th Avenue, Glendale, 85308 AZ, USA

¹¹ Department of Biological Sciences, Cork Institute of Technology, Bishopstown, T12 P928 Cork, Ireland

¹² Departamento de Estructura de Macromoleculas, Centro Nacional de Biotecnologia, Calle Darwin 3, 28049 Madrid, Spain

¹³ Biotechnology Department, Teagasc, Moorepark Food Research Centre, Fermoy, P61 C996 Co. Cork, Ireland

¹⁴ Department of Pharmacognosy, Institute of Pharmacy, University of Innsbruck, Innrain 80-82/IV, 6020 Innsbruck, Austria

¹⁵ Department of Pharmaceutical Botany, Iuliu Hațieganu University of Medicine and Pharmacy, 8 Victor Babes, 400012 Cluj-Napoca, Romania

¹⁶ Department of Natural Drugs, Faculty of Pharmacy, University of Veterinary and Pharmaceutical Sciences Brno, Palackého 1, 61242 Brno, Czech Republic

¹⁷ Department of Pharmacy, College of Pharmacy, Seoul National University, 1 Gwanak-ro, 08826 Seoul, Korea

¹⁸ Institute of Chemistry, University of Silesia, Szkolna 9, 40007 Katowice, Poland

¹⁹ Faculty of Chemistry and Chemical Technology, University of Ljubljana, Večna pot 113, 1000 Ljubljana, Slovenia

²⁰ Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Comenius University, Odbojárov 10, 83232 Bratislava, Slovakia

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Molecules 2016, 21(10), 1381; https://doi.org/10.3390/molecules21101381 - 17 Oct 2016

Cited by 5 | Viewed by 9538

Abstract

The Eighth Central European Conference “Chemistry towards Biology” was held in Brno, Czech Republic, on August 28–September 1, 2016 to bring together experts in biology, chemistry and design of bioactive compounds; promote the exchange of scientific results, methods and ideas; and encourage cooperation [...] Read more.

The Eighth Central European Conference “Chemistry towards Biology” was held in Brno, Czech Republic, on August 28–September 1, 2016 to bring together experts in biology, chemistry and design of bioactive compounds; promote the exchange of scientific results, methods and ideas; and encourage cooperation between researchers from all over the world. The topics of the conference covered “Chemistry towards Biology”, meaning that the event welcomed chemists working on biology-related problems, biologists using chemical methods, and students and other researchers of the respective areas that fall within the common scope of chemistry and biology. The authors of this manuscript are plenary speakers and other participants of the symposium and members of their research teams. The following summary highlights the major points/topics of the meeting. Full article

(This article belongs to the Special Issue Selected Papers from the 8th Central European Conference ‘Chemistry towards Biology’ (CTB-2016))

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12 pages, 2560 KiB

Open AccessArticle

Towards Water Soluble Mitochondria-Targeting Theranostic Osmium(II) Triazole-Based Complexes

by Salem A. E. Omar¹

, Paul A. Scattergood¹, Luke K. McKenzie^2,3

, Helen E. Bryant³, Julia A. Weinstein² and Paul I. P. Elliott^1,*

¹ Department of Chemistry, University of Huddersfield, Queensgate, Huddersfield HD1 3DH, UK

² Department of Chemistry, Dainton Building, University of Sheffield, Sheffield S3 7HF, UK

³ Academic Unit of Molecular Oncology, Sheffield Institute for Nucleic Acids (SInFoNiA), Department of Oncology and Metabolism, University of Sheffield, Beech Hill Road, Sheffield S10 2RX, UK

Molecules 2016, 21(10), 1382; https://doi.org/10.3390/molecules21101382 - 18 Oct 2016

Cited by 20 | Viewed by 8179

Abstract

The complex [Os(btzpy)₂][PF₆]₂ (1, btzpy = 2,6-bis(1-phenyl-1,2,3-triazol-4-yl)pyridine) has been prepared and characterised. Complex 1 exhibits phosphorescence (λ_em = 595 nm, τ = 937 ns, φ_em = 9.3% in degassed acetonitrile) in contrast to its [...] Read more.

The complex [Os(btzpy)₂][PF₆]₂ (1, btzpy = 2,6-bis(1-phenyl-1,2,3-triazol-4-yl)pyridine) has been prepared and characterised. Complex 1 exhibits phosphorescence (λ_em = 595 nm, τ = 937 ns, φ_em = 9.3% in degassed acetonitrile) in contrast to its known ruthenium(II) analogue, which is non-emissive at room temperature. The complex undergoes significant oxygen-dependent quenching of emission with a 43-fold reduction in luminescence intensity between degassed and aerated acetonitrile solutions, indicating its potential to act as a singlet oxygen sensitiser. Complex 1 underwent counterion metathesis to yield [Os(btzpy)₂]Cl₂ (1^Cl), which shows near identical optical absorption and emission spectra to those of 1. Direct measurement of the yield of singlet oxygen sensitised by 1^Cl was carried out (φ (¹O₂) = 57%) for air equilibrated acetonitrile solutions. On the basis of these photophysical properties, preliminary cellular uptake and luminescence microscopy imaging studies were conducted. Complex 1^Cl readily entered the cancer cell lines HeLa and U2OS with mitochondrial staining seen and intense emission allowing for imaging at concentrations as low as 1 μM. Long-term toxicity results indicate low toxicity in HeLa cells with LD50 >100 μM. Osmium(II) complexes based on 1 therefore present an excellent platform for the development of novel theranostic agents for anticancer activity. Full article

(This article belongs to the Special Issue Recent Advances in CuAAC Click Chemistry)

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13 pages, 7385 KiB

Open AccessArticle

Deep Eutectic Solvent-Based Microwave-Assisted Method for Extraction of Hydrophilic and Hydrophobic Components from Radix Salviae miltiorrhizae

by Jue Chen^1,2, Mengjun Liu¹, Qi Wang¹, Huizhi Du¹ and Liwei Zhang^1,*

¹ Institute of Molecule Science, Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Shanxi University, Taiyuan 030006, China

² Modern Research Center for Traditional Chinese Medicine, Shanxi University, Taiyuan 030006, Shanxi, China

Molecules 2016, 21(10), 1383; https://doi.org/10.3390/molecules21101383 - 17 Oct 2016

Cited by 68 | Viewed by 9094

Abstract

Deep eutectic solvents (DESs) have attracted significant attention as a promising green media. In this work, twenty-five kinds of benign choline chloride-based DESs with microwave-assisted methods were applied to quickly extract active components from Radix Salviae miltiorrhizae. The extraction factors, including temperature, [...] Read more.

Deep eutectic solvents (DESs) have attracted significant attention as a promising green media. In this work, twenty-five kinds of benign choline chloride-based DESs with microwave-assisted methods were applied to quickly extract active components from Radix Salviae miltiorrhizae. The extraction factors, including temperature, time, power of microwave, and solid/liquid ratio, were investigated systematically by response surface methodology. The hydrophilic and hydrophobic ingredients were extracted simultaneously under the optimized conditions: 20 vol% of water in choline chloride/1,2-propanediol (1:1, molar ratio) as solvent, microwave power of 800 W, temperature at 70 °C, time at 11.11 min, and solid/liquid ratio of 0.007 g·mL⁻¹. The extraction yield was comparable to, or even better than, conventional methods with organic solvents. The microstructure alteration of samples before and after extraction was also investigated. The method validation was tested as the linearity of analytes (r² > 0.9997 over two orders of magnitude), precision (intra-day relative standard deviation (RSD) < 2.49 and inter-day RSD < 2.96), and accuracy (recoveries ranging from 95.04% to 99.93%). The proposed DESs combined with the microwave-assisted method provided a prominent advantage for fast and efficient extraction of active components, and DESs could be extended as solvents to extract and analyze complex environmental and pharmaceutical samples. Full article

(This article belongs to the Special Issue Ionic Liquids and Deep Eutectic Solvents for Synthesis, Materials and Energy)

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13 pages, 1039 KiB

Open AccessArticle

Bioanalytical Method Development Using Liquid Chromatography with Amperometric Detection for the Pharmacokinetic Evaluation of Forsythiaside in Rats

by Yu-Tse Wu^1,*

, Meng-Ting Cai¹, Chih-Wei Chang¹

, Ching-Chi Yen¹ and Mei-Chich Hsu²

¹ School of Pharmacy, Kaohsiung Medical University, Kaohsiung 807, Taiwan

² Department of Sports Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan

Molecules 2016, 21(10), 1384; https://doi.org/10.3390/molecules21101384 - 16 Oct 2016

Cited by 4 | Viewed by 5023

Abstract

An analytical method entailing high-performance liquid chromatography coupled with electrochemical detection was developed for determining forsythiaside (FTS) in rat plasma. Rat plasma samples were prepared through efficient trichloroacetic acid deproteination. FTS and the internal standard were chromatographically separated on a reversed-phase core-shell silica [...] Read more.

An analytical method entailing high-performance liquid chromatography coupled with electrochemical detection was developed for determining forsythiaside (FTS) in rat plasma. Rat plasma samples were prepared through efficient trichloroacetic acid deproteination. FTS and the internal standard were chromatographically separated on a reversed-phase core-shell silica C18 column (100 mm × 2.1 mm, i.d. 2.6 μm), with a mobile phase consisting of an acetonitrile—0.05-M phosphate solution (11.8:88.2, v/v), at a flow rate of 400 μL/min. The calibration curve, with r² > 0.999, was linear in the 20–1000 ng/mL range. The intra- and interday precision were less than 9.0%, and the accuracy ranged from 94.5% to 106.5% for FTS. The results indicated that the newly developed HPLC-EC method is more sensitive than previous reported methods using UV detection, and this new analytical method is applied successfully for the pharmacokinetic study of FTS. The hydrogel delivery system can efficiently improve bioavailability and mean residual time for FTS, as evidenced by the 2.5- and 6.3-fold increase of the area under the curve and the extension of the half-life, respectively. Full article

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11 pages, 1062 KiB

Open AccessArticle

New Sesquiterpenoids and Anti-Platelet Aggregation Constituents from the Rhizomes of Curcuma zedoaria

by Jih-Jung Chen^1,2,*,†

, Tung-Han Tsai¹, Hsiang-Ruei Liao^3,†, Li-Chai Chen^1,4,†, Yueh-Hsiung Kuo^5,6,†

, Ping-Jyun Sung⁷

, Chun-Lin Chen⁸

and Chun-Sheng Wei^4,†

¹ Department of Pharmacy, Tajen University, Pingtung 907, Taiwan

² Department of Medical Research, China Medical University Hospital, China Medical University, Taichung 404, Taiwan

³ Graduate Institute of Natural Products, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan

⁴ Department of Pharmacy, Zuoying Branch of Kaohsiung Armed Forces General Hospital, Kaohsiung 813, Taiwan

⁵ Department of Chinese Pharmaceutical Sciences and Chinese Medicine Resources, China Medical University, Taichung 404, Taiwan

⁶ Department of Biotechnology, Asia University, Taichung 413, Taiwan

⁷ National Museum of Marine Biology and Aquarium, Pingtung 944, Taiwan

⁸ Department of Biological Sciences, National Sun Yat-sen University, Kaohsiung 804, Taiwan

^† These authors contributed equally to this work.

Molecules 2016, 21(10), 1385; https://doi.org/10.3390/molecules21101385 - 17 Oct 2016

Cited by 26 | Viewed by 6266

Abstract

Two new sesquiterpenoids—13-hydroxycurzerenone (1) and 1-oxocurzerenone (2)—have been isolated from the rhizomes of Curcuma zedoaria, together with 13 known compounds (3–15). The structures of two new compounds were determined through spectroscopic and MS analyses. [...] Read more.

Two new sesquiterpenoids—13-hydroxycurzerenone (1) and 1-oxocurzerenone (2)—have been isolated from the rhizomes of Curcuma zedoaria, together with 13 known compounds (3–15). The structures of two new compounds were determined through spectroscopic and MS analyses. Among the isolated compounds, 13-hydroxycurzerenone (1), 1-oxocurzerenone (2), curzerenone (3), germacrone (4), curcolone (5), procurcumenol (6), ermanin (7), curcumin (8), and a mixture of stigmast-4-en-3,6-dione (12) and stigmasta-4,22-dien-3,6-dione (13) exhibited inhibition (with inhibition % in the range of 21.28%–67.58%) against collagen-induced platelet aggregation at 100 μM. Compounds 1, 5, 7, 8, and the mixture of 12 and 13 inhibited arachidonic acid (AA)-induced platelet aggregation at 100 μM with inhibition % in the range of 23.44%–95.36%. Full article

(This article belongs to the Section Natural Products Chemistry)

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16 pages, 3991 KiB

Open AccessArticle

Characterization, in Vivo and in Vitro Evaluation of Solid Dispersion of Curcumin Containing d-α-Tocopheryl Polyethylene Glycol 1000 Succinate and Mannitol

by Im-Sook Song¹, Jin-Sun Cha² and Min-Koo Choi^2,*

¹ College of Pharmacy and Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu 41566, Korea

² College of Pharmacy, Dankook University, Cheon-an 31116, Korea

Molecules 2016, 21(10), 1386; https://doi.org/10.3390/molecules21101386 - 17 Oct 2016

Cited by 55 | Viewed by 7458

Abstract

The aim of this study was to prepare a solid dispersion formulation of curcumin to enhance its solubility, dissolution rate, and oral bioavailability. The formulation was prepared with d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) and mannitol using solvent evaporation and freeze-drying methods, [...] Read more.

The aim of this study was to prepare a solid dispersion formulation of curcumin to enhance its solubility, dissolution rate, and oral bioavailability. The formulation was prepared with d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) and mannitol using solvent evaporation and freeze-drying methods, which yielded a solid dispersion composed of curcumin, TPGS, and mannitol at a ratio of 1:10:15 (w/w/w). The solubility and dissolution rate of the curcumin solid dispersion markedly improved compared with those of curcumin powder and a physical mixture of curcumin, TPGS, and mannitol. About 90% of the curcumin was released from the solid dispersion formulation within 10 min. After administering the formulation orally to rats, higher plasma concentrations of curcumin were observed, with increases in the maximum plasma concentration (C_max) and area under the plasma concentration-time curve (AUC) of 86- and 65-fold, respectively, compared with those of curcumin powder. The solid dispersion formulation effectively increased intestinal permeability and inhibited P-gp function. These effects increased the anti-proliferative effect of curcumin in MDA-MB-231 breast cancer cells. Moreover, 2 h incubation with curcumin powder, solid dispersion formulation, and its physical mixture resulted in differential cytotoxic effect of paclitaxel in P-gp overexpressed LLC-PK1-P-gp and MDA-MB-231 cells through the inhibition of P-gp-mediated paclitaxel efflux. In conclusion, compared with curcumin, a solid dispersion formulation of curcumin with TPGS and mannitol could be a promising option for enhancing the oral bioavailability and efficacy of curcumin through increased solubility, dissolution rate, cell permeability, and P-gp modulation. Full article

(This article belongs to the Collection Poorly Soluble Drugs)

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11 pages, 996 KiB

Open AccessArticle

Design, Synthesis and Antifungal Activity of Coumarin Ring-Opening Derivatives

by Ming-Zhi Zhang

, Yu Zhang, Jia-Qun Wang and Wei-Hua Zhang^*

Jiangsu Key Laboratory of Pesticide Science, College of Sciences, Nanjing Agricultural University, Nanjing 210095, China

Molecules 2016, 21(10), 1387; https://doi.org/10.3390/molecules21101387 - 17 Oct 2016

Cited by 22 | Viewed by 7313

Abstract

Based on our initial design, we synthesized two series of coumarin ring-opening derivatives by the reactions of hydrolysis and methylation. Results of antifungal screening in vitro showed that the target compounds exhibited potent activity against the six common pathogenic fungi. Compounds 6b, [...] Read more.

Based on our initial design, we synthesized two series of coumarin ring-opening derivatives by the reactions of hydrolysis and methylation. Results of antifungal screening in vitro showed that the target compounds exhibited potent activity against the six common pathogenic fungi. Compounds 6b, 6e, 6g, 6i, 7b and 7c were identified as the most active ones, and the EC₅₀ values of these active compounds were further tested. Compared to the commonly used fungicide Azoxystrobin (0.0884 µM), compounds 6b (0.0544 µM) and 6e (0.0823 µM) displayed improved activity against Botrytis cinerea. Full article

(This article belongs to the Special Issue Natural Product Inspired Scaffolds Designs)

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15 pages, 6151 KiB

Open AccessArticle

Decrystallization of Crystals Using Gold “Nano-Bullets” and the Metal-Assisted and Microwave-Accelerated Decrystallization Technique

by Nishone Thompson¹, Zainab Boone-Kukoyi¹, Raquel Shortt¹, Carisse Lansiquot¹, Bridgit Kioko¹, Enock Bonyi¹, Salih Toker¹, Birol Ozturk² and Kadir Aslan^1,*

¹ Department of Chemistry, Morgan State University, 1700 East Cold Spring Lane, Baltimore, MD 21251, USA

² Department of Physics and Engineering Physics, Morgan State University, 1700 East Cold Spring Lane, Baltimore, MD 21251, USA

Molecules 2016, 21(10), 1388; https://doi.org/10.3390/molecules21101388 - 18 Oct 2016

Cited by 3 | Viewed by 6982

Abstract

Gout is caused by the overproduction of uric acid and the inefficient metabolism of dietary purines in humans. Current treatments of gout, which include anti-inflammatory drugs, cyclooxygenase-2 inhibitors, and systemic glucocorticoids, have harmful side-effects. Our research laboratory has recently introduced an innovative approach [...] Read more.

Gout is caused by the overproduction of uric acid and the inefficient metabolism of dietary purines in humans. Current treatments of gout, which include anti-inflammatory drugs, cyclooxygenase-2 inhibitors, and systemic glucocorticoids, have harmful side-effects. Our research laboratory has recently introduced an innovative approach for the decrystallization of biological and chemical crystals using the Metal-Assisted and Microwave-Accelerated Evaporative Decrystallization (MAMAD) technique. In the MAMAD technique, microwave energy is used to heat and activate gold nanoparticles that behave as “nano-bullets” to rapidly disrupt the crystal structure of biological crystals placed on planar surfaces. In this study, crystals of various sizes and compositions were studied as models for tophaceous gout at different stages (i.e., uric acid as small crystals (~10–100 μm) and l-alanine as medium (~300 μm) and large crystals (~4400 μm). Our results showed that the use of the MAMAD technique resulted in the reduction of the size and number of uric acid and l-alanine crystals up to >40% when exposed to intermittent microwave heating (up to 20 W power at 8 GHz) in the presence of 20 nm gold nanoparticles up to 120 s. This study demonstrates that the MAMAD technique can be potentially used as an alternative therapeutic method for the treatment of gout by effective decrystallization of large crystals, similar in size to those that often occur in gout. Full article

(This article belongs to the Special Issue Gold Nanoparticles for Biomedical Applications)

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48 pages, 5610 KiB

Open AccessReview

The Potential of Secondary Metabolites from Plants as Drugs or Leads against Protozoan Neglected Diseases—Part III: In-Silico Molecular Docking Investigations

by Ifedayo Victor Ogungbe¹

and William N. Setzer^2,*

¹ Department of Chemistry and Biochemistry, Jackson State University, Jackson, MS 39217, USA

² Department of Chemistry, University of Alabama in Huntsville, Huntsville, AL 35899, USA

Molecules 2016, 21(10), 1389; https://doi.org/10.3390/molecules21101389 - 19 Oct 2016

Cited by 38 | Viewed by 13200

Abstract

Malaria, leishmaniasis, Chagas disease, and human African trypanosomiasis continue to cause considerable suffering and death in developing countries. Current treatment options for these parasitic protozoal diseases generally have severe side effects, may be ineffective or unavailable, and resistance is emerging. There is a [...] Read more.

Malaria, leishmaniasis, Chagas disease, and human African trypanosomiasis continue to cause considerable suffering and death in developing countries. Current treatment options for these parasitic protozoal diseases generally have severe side effects, may be ineffective or unavailable, and resistance is emerging. There is a constant need to discover new chemotherapeutic agents for these parasitic infections, and natural products continue to serve as a potential source. This review presents molecular docking studies of potential phytochemicals that target key protein targets in Leishmania spp., Trypanosoma spp., and Plasmodium spp. Full article

(This article belongs to the Collection Natural Products as Leads or Drugs against Neglected Tropical Diseases)

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17 pages, 4248 KiB

Open AccessArticle

by Ellen Games¹, Marina Guerreiro¹, Fernanda R. Santana¹

, Nathalia M. Pinheiro², Emerson A. De Oliveira¹, Fernanda D.T.Q.S. Lopes², Clarice R. Olivo², Iolanda F.L.C. Tibério², Mílton A. Martins², João Henrique G. Lago^3,4 and Carla M. Prado^5,*

¹ Department of Biological Science, Universidade Federal de São Paulo, Diadema 09913-030, Brazil

² Department of Medicine, School of Medicine, Universidade de São Paulo, São Paulo 01246903, SP, Brazil

³ Department of Exact Science and Earth, Universidade Federal de São Paulo, Diadema 09913-030, Brazil

⁴ Center of Natural Sciences and Humanities, Federal University of ABC, Santo Andre 09606-045, SP, Brazil

⁵ Department of Bioscience, Federal University of São Paulo, Campus Baixada Santista, Santos 11015-020, SP, Brazil

Molecules 2016, 21(10), 1390; https://doi.org/10.3390/molecules21101390 - 20 Oct 2016

Cited by 51 | Viewed by 12215

Abstract

Background: Chronic obstructive pulmonary disease (COPD) is characterized by irreversible airflow obstruction and inflammation. Natural products, such as monoterpenes, displayed anti-inflammatory and anti-oxidant activities and can be used as a source of new compounds to COPD treatment. Our aim was to evaluate, in [...] Read more.

Background: Chronic obstructive pulmonary disease (COPD) is characterized by irreversible airflow obstruction and inflammation. Natural products, such as monoterpenes, displayed anti-inflammatory and anti-oxidant activities and can be used as a source of new compounds to COPD treatment. Our aim was to evaluate, in an elastase-induced pulmonary emphysema in mice, the effects of and underlying mechanisms of three related natural monoterpenes (p-cymene, carvacrol and thymol) isolated from essential oil from leaves Lippia sidoides Cham. (Verbenaceae). Methods: Mices received porcine pancreatic elastase (PPE) and were treated with p-cymene, carvacrol, thymol or vehicle 30 min later and again on 7th, 14th and 28th days. Lung inflammatory profile and histological sections were evaluated. Results: In the elastase-instilled animals, the tested monoterpenes reduced alveolar enlargement, macrophages and the levels of IL-1β, IL-6, IL-8 and IL-17 in bronchoalveolar lavage fluid (BALF), and collagen fibers, MMP-9 and p-65-NF-κB-positive cells in lung parenchyma (p < 0.05). All treatments attenuated levels of 8-iso-PGF2α but only thymol was able to reduced exhaled nitric oxide (p < 0.05). Conclusion: Monoterpenes p-cymene, carvacrol and thymol reduced lung emphysema and inflammation in mice. No significant differences among the three monoterpenes treatments were found, suggesting that the presence of hydroxyl group in the molecular structure of thymol and carvacrol do not play a central role in the anti-inflammatory effects. Full article

(This article belongs to the Special Issue Natural Products and Inflammation)

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11 pages, 11987 KiB

Open AccessArticle

Renal Protective Effects of 17β-Estradiol on Mice with Acute Aristolochic Acid Nephropathy

by Min Shi¹, Liang Ma^1,2

, Li Zhou^1,2,*

and Ping Fu^1,2,*

¹ Division of Nephrology, Department of Internal Medicine, West China Hospital of Sichuan University, Chengdu 610041, Sichuan, China

² Kidney Research Institute, West China Hospital of Sichuan University, Chengdu 610041, Sichuan, China

Molecules 2016, 21(10), 1391; https://doi.org/10.3390/molecules21101391 - 18 Oct 2016

Cited by 26 | Viewed by 6642

Abstract

Aristolochic acid nephropathy (AAN) is a progressive kidney disease caused by a Chinese herb containing aristolochic acid. Excessive death of renal tubular epithelial cells (RTECs) characterized the acute phase of AAN. Therapies for acute AAN were limited, such as steroids and angiotensin-receptor blockers [...] Read more.

Aristolochic acid nephropathy (AAN) is a progressive kidney disease caused by a Chinese herb containing aristolochic acid. Excessive death of renal tubular epithelial cells (RTECs) characterized the acute phase of AAN. Therapies for acute AAN were limited, such as steroids and angiotensin-receptor blockers (ARBs)/angiotensin-converting enzyme inhibitors (ACEIs). It was interesting that, in acute AAN, female patients showed relative slower progression to renal failure than males. In a previous study, female hormone 17β-estradiol (E2) was found to attenuate renal ischemia-reperfusion injury. Thus, the aim of this study was to investigate the potential protective role of E2 in acute AAN. Compared with male C57BL/6 mice of acute AAN, lower serum creatinine (SCr) and less renal injury, together with RTEC apoptosis in females, were found. Treatment with E2 in male AAN mice reduced SCr levels and attenuated renal tubular injury and RTEC apoptosis. In the mice kidney tissue and human renal proximal tubule cells (HK-2 cells), E2 both attenuated AA-induced cell apoptosis and downregulated the expression of phosphor-p53 (Ser15), p53, and cleaved-caspase-3. This study highlights that E2 exhibited protective effects on the renal injury of acute AAN in male mice by reducing RTEC apoptosis, which might be related to inhibiting the p53 signaling pathway. Full article

(This article belongs to the Section Medicinal Chemistry)

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14 pages, 4743 KiB

Open AccessArticle

Application of Super-Amphiphilic Silica-Nanogel Composites for Fast Removal of Water Pollutants

by Ayman M. Atta^1,2,*, Hamad A. Al-Lohedan¹

, Ahmed M. Tawfik² and Abdelrahman O. Ezzat¹

¹ Chemistry Department, College of Science, King Saud University, Riyadh 11541, Saudi Arabia

² College of Science, King Saud University, Riyadh 11541, Saudi Arabia

Molecules 2016, 21(10), 1392; https://doi.org/10.3390/molecules21101392 - 19 Oct 2016

Cited by 16 | Viewed by 8047

Abstract

This work first reports the preparation of super-amphiphilic silica-nanogel composites to reduce the contact angle of water to increase the diffusion of pollutant into adsorbents. In this respect, the silica nanoparticles were encapsulated into nanogels based on ionic and nonionic polyacrylamides by dispersion [...] Read more.

This work first reports the preparation of super-amphiphilic silica-nanogel composites to reduce the contact angle of water to increase the diffusion of pollutant into adsorbents. In this respect, the silica nanoparticles were encapsulated into nanogels based on ionic and nonionic polyacrylamides by dispersion polymerization technique. The morphologies and the dispersion stability of nanogel composites were investigated to clarify the ability of silica-nanogel composites to adsorb at different interfaces. The feasibility of silica polyacrylamide nanogel composites to act as a high-performance adsorbent for removal of methylene blue (MB) dye and heavy metals (Co²⁺ and Ni²⁺) from aqueous solution was investigated. The surface tension, contact angle, average pore size, and zeta potential of the silica-nanogel composites have been evaluated. The MB dye and heavy metal adsorption capacity achieved Q_max = 438–387 mg/g which is considerably high. The adsorption capacity results are explained from the changes in the morphology of the silica surfaces as recorded from scanning electron microscopy (SEM). Full article

(This article belongs to the Section Molecular Diversity)

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22 pages, 3330 KiB

Open AccessReview

Development and Applications of the Copper-Catalyzed Azide-Alkyne Cycloaddition (CuAAC) as a Bioorthogonal Reaction

by Li Li^1,2 and Zhiyuan Zhang^2,*

¹ School of Life Sciences, Peking University, Beijing 100871, China

² National Institute of Biological Sciences, Beijing 102206, China

Molecules 2016, 21(10), 1393; https://doi.org/10.3390/molecules21101393 - 24 Oct 2016

Cited by 158 | Viewed by 19712

Abstract

The emergence of bioorthogonal reactions has greatly broadened the scope of biomolecule labeling and detecting. Of all the bioorthogonal reactions that have been developed, the copper-catalyzed azide-alkyne cycloaddition (CuAAC) is the most widely applied one, mainly because of its relatively fast kinetics and [...] Read more.

The emergence of bioorthogonal reactions has greatly broadened the scope of biomolecule labeling and detecting. Of all the bioorthogonal reactions that have been developed, the copper-catalyzed azide-alkyne cycloaddition (CuAAC) is the most widely applied one, mainly because of its relatively fast kinetics and high efficiency. However, the introduction of copper species to in vivo systems raises the issue of potential toxicity. In order to reduce the copper-induced toxicity and further improve the reaction kinetics and efficiency, different strategies have been adopted, including the development of diverse copper chelating ligands to assist the catalytic cycle and the development of chelating azides as reagents. Up to now, the optimization of CuAAC has facilitated its applications in labeling and identifying either specific biomolecule species or on the omics level. Herein, we mainly discuss the efforts in the development of CuAAC to better fit the bioorthogonal reaction criteria and its bioorthogonal applications both in vivo and in vitro. Full article

(This article belongs to the Special Issue Recent Advances in CuAAC Click Chemistry)

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14 pages, 3583 KiB

Open AccessArticle

Adsorption of Wine Constituents on Functionalized Surfaces

by Agnieszka Mierczynska-Vasilev^* and Paul A. Smith

The Australian Wine Research Institute, P.O. Box 197, Glen Osmond, Adelaide 5064, South Australia, Australia

Molecules 2016, 21(10), 1394; https://doi.org/10.3390/molecules21101394 - 18 Oct 2016

Cited by 11 | Viewed by 5792

Abstract

The adsorption of macromolecules on solid surfaces is of great importance in the field of nanotechnology, biomaterials, biotechnological, and food processes. In the field of oenology adsorption of wine macromolecules such as polyphenols, polysaccharides, and proteins is much less desirable on membrane materials [...] Read more.

The adsorption of macromolecules on solid surfaces is of great importance in the field of nanotechnology, biomaterials, biotechnological, and food processes. In the field of oenology adsorption of wine macromolecules such as polyphenols, polysaccharides, and proteins is much less desirable on membrane materials because of fouling and reduced filtering performance. On the other hand, adsorption of these molecules on processing aids is very beneficial for achieving wine clarity and stability. In this article, the effect of surface chemical functionalities on the adsorption of white, rosé, and red wine constituents was evaluated. Allylamine, acrylic acid, and ethanol were selected as precursors for plasma polymerization in order to generate coatings rich in amine, carboxyl, and hydroxyl chemical groups, respectively. The surface chemical functionalities were characterized by X-ray photoelectron spectroscopy (XPS) and the ability of different surface chemical functionalities to adsorb wine constituents were characterized by quartz crystal microbalance with dissipation (QCM-D) and atomic force microscopy (AFM). The results demonstrated that the amine and carboxyl modified surfaces encourage adsorption of constituents from white wine. The hydroxyl modified surfaces have the ability to preferentially adsorb rosé wine constituents, whereas red wine adsorbed to the highest extent on acrylic acid surface. Full article

(This article belongs to the Collection Wine Chemistry)

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17 pages, 1915 KiB

Open AccessArticle

Improved Production and Antitumor Properties of Triterpene Acids from Submerged Culture of Ganoderma lingzhi

by Xiao-Ling Wang^1,2, Zhong-Yang Ding³, Gao-Qiang Liu^1,2,*, Hailong Yang⁴ and Guo-Ying Zhou^1,2

¹ Key Laboratory of Cultivation and Protection for Non-Wood Forest Trees, Ministry of Education, Central South University of Forestry and Technology, Changsha 410004, China

² Hunan Provincial Key Laboratory for Control of Forest Diseases and Pests, College of Life Science and Technology, Central South University of Forestry & Technology, Changsha 410004, China

³ National Engineering Laboratory for Cereal Fermentation Technology, Jiangnan University, Wuxi 214122, China

⁴ College of Life and Environmental Science, Wenzhou University, Wenzhou 325035, China

Molecules 2016, 21(10), 1395; https://doi.org/10.3390/molecules21101395 - 20 Oct 2016

Cited by 15 | Viewed by 6186

Abstract

Triterpene acids (TAs) are the major bioactive constituents in the medicinal fungus Ganoderma lingzhi. However, fermentative production of TAs has not been optimized for commercial use, and whether the TAs isolated from G. lingzhi submerged culture mycelia possess antitumor activity needs to [...] Read more.

Triterpene acids (TAs) are the major bioactive constituents in the medicinal fungus Ganoderma lingzhi. However, fermentative production of TAs has not been optimized for commercial use, and whether the TAs isolated from G. lingzhi submerged culture mycelia possess antitumor activity needs to be further proven. In this study, enhanced TA yield and productivity were attained with G. lingzhi using response surface methodology. The interactions of three variables were studied using a Box-Benhnken design, namely initial pH, dissolved oxygen (DO) and fermentation temperature. The optimum conditions were an initial pH of 5.9, 20.0% DO and 28.6 °C. These conditions resulted in a TA yield of 308.1 mg/L in a 5-L stirred bioreactor. Furthermore, the optimized conditions were then successfully scaled up to a production scale of 200 L, and maximum TA production and productivity of 295.3 mg/L and 49.2 mg/L/day were achieved, which represented 80.9% and 111.5% increases, respectively, compared with the non-optimized conditions. Additionally, the triterpene acid extract (TAE) from G. lingzhi mycelia was found to be cytotoxic to the SMMC-7721 and SW620 cell lines in vitro, and the TAE exhibited dose-dependent antitumor activity against the solid tumor sarcoma 180 in vivo. Chemical analysis revealed that the key active triterpene compounds, ganoderic acid T and ganoderic acid Me, predominated in the extract. Full article

(This article belongs to the Section Natural Products Chemistry)

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21 pages, 3887 KiB

Open AccessArticle

20(S)-Protopanaxadiol Phospholipid Complex: Process Optimization, Characterization, In Vitro Dissolution and Molecular Docking Studies

by Yiqiong Pu¹, Xitong Zhang², Qi Zhang², Bing Wang^1,2,*

, Yuxi Chen², Chuanqi Zang², Yuqin Wang³, Tina Ting-Xia Dong⁴ and Tong Zhang^1,2,*

¹ Experiment Center for Teaching and Learning, Shanghai University of Traditional Chinese Medicine, No. 1200 Cailun Road, Pudong New District, Shanghai 201203, China

² School of Pharmacy, Shanghai University of Traditional Chinese Medicine, No. 1200 Cailun Road, Pudong New District, Shanghai 201203, China

³ Zhejiang BioAsia Institute of Life Science, No. 1938 Xinqun Road, Economic and Technical Development Zone, Pinghu 314200, China

⁴ Division of Life Science and Center for Chinese Medicine, The Hong Kong University of Science and Technology, Clear Water Bay Road, Hong Kong, China

Molecules 2016, 21(10), 1396; https://doi.org/10.3390/molecules21101396 - 19 Oct 2016

Cited by 28 | Viewed by 7635

Abstract

20(S)-Protopanaxadiol (PPD), a bioactive compound extracted from ginseng, possesses cardioprotective, neuroprotective, anti-inflammatory, antiestrogenic, anticancer and anxiolytic effects. However, the clinical application of PPD is limited by its weak aqueous solubility. In this study, we optimized an efficient method of preparing its [...] Read more.

20(S)-Protopanaxadiol (PPD), a bioactive compound extracted from ginseng, possesses cardioprotective, neuroprotective, anti-inflammatory, antiestrogenic, anticancer and anxiolytic effects. However, the clinical application of PPD is limited by its weak aqueous solubility. In this study, we optimized an efficient method of preparing its phospholipid complex (PPD-PLC) using a central composite design and response surface analysis. The prepared PPD-PLC was characterized by differential scanning calorimetric, powder X-ray diffraction, Fourier-transformed infrared spectroscopy and nuclear magnetic resonance analyses associated with molecular docking calculation. The equilibrium solubility of PPD-PLC in water and n-octanol increased 6.53- and 1.53-times, respectively. Afterwards, using PPD-PLC as the intermediate, the PPD-PLC-loaded dry suspension (PPD-PLC-SU) was prepared with our previous method. In vitro evaluations were conducted on PPD-PLC and PPD-PLC-SU, including dissolution behaviors and stability properties under different conditions. Results of in vitro dissolution behavior revealed the improved dissolution extents and rates of PPD-PLC and PPD-PLC-SU (p < 0.05). Results of the formulation stability investigation also exposed the better stability of PPD-PLC-SU compared with free PPD. Therefore, phospholipid complex technology is a useful formulation strategy for BCS II drugs, as it could effectively improve their hydrophilicity and lipophilicity. Full article

(This article belongs to the Section Natural Products Chemistry)

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12 pages, 2353 KiB

Open AccessArticle

Extract from Maize (Zea mays L.): Antibacterial Activity of DIMBOA and Its Derivatives against Ralstonia solanacearum

by Bing Guo^†

, Yongqiang Zhang^†, Shili Li, Ting Lai, Liang Yang, Juanni Chen and Wei Ding^*

¹ Laboratory of Natural Products Pesticides, College of Plant Protection, Southwest University, Chongqing 400715, China

^† These two authors contributed equally to this work.

Molecules 2016, 21(10), 1397; https://doi.org/10.3390/molecules21101397 - 19 Oct 2016

Cited by 24 | Viewed by 8599

Abstract

Many cereals accumulate hydroxamic acids involved in defense of plant against various fungi, bacteria, and insects. 2,4-dihydroxy-7-methoxy-1,4-benzoxazine-3-one, commonly known as DIMBOA, is one of the principal cyclic hydroxamic acids in aqueous extracts of maize. The aim of this study was to evaluate the [...] Read more.

Many cereals accumulate hydroxamic acids involved in defense of plant against various fungi, bacteria, and insects. 2,4-dihydroxy-7-methoxy-1,4-benzoxazine-3-one, commonly known as DIMBOA, is one of the principal cyclic hydroxamic acids in aqueous extracts of maize. The aim of this study was to evaluate the antibacterial activity of the isolated DIMBOA and its derivatives 2-benzoxazolinone (BOA), 6-chloro-2-benzoxazolinone (CDHB), and 2-mercaptobenzothiazole (MBT) against Ralstonia solanacearum. MBT showed the strongest antibacterial activity, followed by CDHB and DIMBOA, with minimum inhibitory concentrations (MICs) of 50, 100 and 200 mg/L, respectively, better than the BOA with 300 mg/L. These compounds also significantly affect bacterial growth, reduce biofilm formation, and inhibit swarming motility within 24 h. This paper is the first to report the anti-R. solanacearum activity of DIMBOA from Z. mays. The bioassay and pot experiment results suggested that DIMBOA and its derivatives exhibit potential as a new matrix structure of designing target bactericide or elicitor for controlling tobacco bacterial wilt. Further studies must evaluate the efficacy of DIMBOA and its derivatives in controlling bacterial wilt under natural field conditions where low inoculum concentrations exist. Full article

(This article belongs to the Collection Antibiotics & Superbugs: New Strategies to Combat Antimicrobial Resistance)

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13 pages, 1567 KiB

Open AccessArticle

Proteome and Peptidome of Vipera berus berus Venom

by Aleksandra Bocian^1,*, Małgorzata Urbanik¹, Konrad Hus¹

, Andrzej Łyskowski¹

, Vladimír Petrilla^3,4, Zuzana Andrejčáková³, Monika Petrillová⁵ and Jaroslav Legath^1,2

¹ Department of Biotechnology and Bioinformatics, Faculty of Chemistry, Rzeszow University of Technology, Powstańców Warszawy 6, 35-959 Rzeszów, Poland

² Department of Pharmacology and Toxicology, University of Veterinary Medicine and Pharmacy, Komenského 73, 041 81 Košice, Slovakia

³ Department of Physiology, University of Veterinary Medicine and Pharmacy, Komenského 73, 041 81 Košice, Slovakia

⁴ Zoo Košice, Široká 31, 040 06 Košice-Kavečany, Slovakia

⁵ Department of General Education Subjects, University of Veterinary Medicine and Pharmacy, Komenského 73, 041 81 Košice, Slovakia

Molecules 2016, 21(10), 1398; https://doi.org/10.3390/molecules21101398 - 19 Oct 2016

Cited by 35 | Viewed by 7318

Abstract

Snake venom is a rich source of peptides and proteins with a wide range of actions. Many of the venom components are currently being tested for their usefulness in the treatment of many diseases ranging from neurological and cardiovascular to cancer. It is [...] Read more.

Snake venom is a rich source of peptides and proteins with a wide range of actions. Many of the venom components are currently being tested for their usefulness in the treatment of many diseases ranging from neurological and cardiovascular to cancer. It is also important to constantly search for new proteins and peptides with properties not yet described. The venom of Vipera berus berus has hemolytic, proteolytic and cytotoxic properties, but its exact composition and the factors responsible for these properties are not known. Therefore, an attempt was made to identify proteins and peptides derived from this species venom by using high resolution two-dimensional electrophoresis and MALDI ToF/ToF mass spectrometry. A total of 11 protein classes have been identified mainly proteases but also l-amino acid oxidases, C-type lectin like proteins, cysteine-rich venom proteins and phospholipases A₂ and 4 peptides of molecular weight less than 1500 Da. Most of the identified proteins are responsible for the highly hemotoxic properties of the venom. Presence of venom phospholipases A₂ and l-amino acid oxidases cause moderate neuro-, myo- and cytotoxicity. All successfully identified peptides belong to the bradykinin-potentiating peptides family. The mass spectrometry data are available via ProteomeXchange with identifier PXD004958. Full article

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16 pages, 7883 KiB

Open AccessReview

High-Pressure Design of Advanced BN-Based Materials

by Oleksandr O. Kurakevych¹ and Vladimir L. Solozhenko^2,*

¹ IMPMC, UPMC Sorbonne Universités, UMR CNRS 7590, MNHN, IRD UMR 206, Paris 75005, France

² LSPM–CNRS, Université Paris Nord, Villetaneuse 93430, France

Molecules 2016, 21(10), 1399; https://doi.org/10.3390/molecules21101399 - 20 Oct 2016

Cited by 29 | Viewed by 9772

Abstract

The aim of the present review is to highlight the state of the art in high-pressure design of new advanced materials based on boron nitride. Recent experimental achievements on the governing phase transformation, nanostructuring and chemical synthesis in the systems containing boron nitride [...] Read more.

The aim of the present review is to highlight the state of the art in high-pressure design of new advanced materials based on boron nitride. Recent experimental achievements on the governing phase transformation, nanostructuring and chemical synthesis in the systems containing boron nitride at high pressures and high temperatures are presented. All these developments allowed discovering new materials, e.g., ultrahard nanocrystalline cubic boron nitride (nano-cBN) with hardness comparable to diamond, and superhard boron subnitride B₁₃N₂. Thermodynamic and kinetic aspects of high-pressure synthesis are described based on the data obtained by in situ and ex situ methods. Mechanical and thermal properties (hardness, thermoelastic equations of state, etc.) are discussed. New synthetic perspectives, combining both soft chemistry and extreme pressure–temperature conditions are considered. Full article

(This article belongs to the Special Issue Boron Nitride: Synthesis and Application)

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15 pages, 2301 KiB

Open AccessArticle

Blue Light Emitting Polyphenylene Dendrimers with Bipolar Charge Transport Moieties

by Guang Zhang¹, Manuel Auer-Berger², Dominik W. Gehrig¹, Paul W. M. Blom¹, Martin Baumgarten^1,*, Dieter Schollmeyer³, E. J. W. List-Kratochvil^4,*

and Klaus Müllen^1,*

¹ Max Planck Institute for Polymer Research, Ackermannweg 10, Mainz D-55128, Germany

² Joanneum Research Materials, Institut für Oberflächentechnologien und Photonik, Franz-Pichler-Straße 30, Weiz 8160, Austria

³ Institute für Organische Chemie, Johannes Gutenberg-Universität, Mainz D-55128, Germany

⁴ Institut für Physik, Institut für Chemie, Humboldt-Universität zu Berlin, IRIS Adlershof, Unter den Linden 6, Berlin 10099, Germany

Molecules 2016, 21(10), 1400; https://doi.org/10.3390/molecules21101400 - 20 Oct 2016

Cited by 13 | Viewed by 9442

Abstract

Two light-emitting polyphenylene dendrimers with both hole and electron transporting moieties were synthesized and characterized. Both molecules exhibited pure blue emission solely from the pyrene core and efficient surface-to-core energy transfers when characterized in a nonpolar environment. In particular, the carbazole- and oxadiazole-functionalized [...] Read more.

Two light-emitting polyphenylene dendrimers with both hole and electron transporting moieties were synthesized and characterized. Both molecules exhibited pure blue emission solely from the pyrene core and efficient surface-to-core energy transfers when characterized in a nonpolar environment. In particular, the carbazole- and oxadiazole-functionalized dendrimer (D1) manifested a pure blue emission from the pyrene core without showing intramolecular charge transfer (ICT) in environments with increasing polarity. On the other hand, the triphenylamine- and oxadiazole-functionalized one (D2) displayed notable ICT with dual emission from both the core and an ICT state in highly polar solvents. D1, in a three-layer organic light emitting diode (OLED) by solution processing gave a pure blue emission with Commission Internationale de l’Éclairage 1931 CIE xy = (0.16, 0.12), a peak current efficiency of 0.21 cd/A and a peak luminance of 2700 cd/m². This represents the first reported pure blue dendrimer emitter with bipolar charge transport and surface-to-core energy transfer in OLEDs. Full article

(This article belongs to the Special Issue Organic Light Emitting Diodes)

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14 pages, 4209 KiB

Open AccessArticle

Curcumin Shows Antiviral Properties against Norovirus

by Minji Yang^1,†, GilJae Lee^1,†, Jiyeon Si¹, Sung-Joon Lee², Hyun Ju You^1,4,* and GwangPyo Ko^1,3,*

¹ Department of Environmental Health Sciences, Graduate School of Public Health, Seoul National University, Seoul 151-742, Korea

² Department of Biotechnology, Graduate School of Life Sciences and Biotechnology, Department of Food Biosciences and Technology, College of Life Sciences and Biotechnology, Korea University, Seoul 151-742, Korea

³ N-Bio, Seoul National University, Seoul 151-742, Korea

⁴ Institute of Health and Environment, Seoul National University, Seoul 151-742, Korea

^† These authors contributed equally to this work.

Molecules 2016, 21(10), 1401; https://doi.org/10.3390/molecules21101401 - 20 Oct 2016

Cited by 55 | Viewed by 9510

Abstract

Phytochemicals provide environmentally friendly and relatively inexpensive natural products, which could potentially benefit public health by controlling human norovirus (HuNoV) infection. In this study, 18 different phytochemicals were evaluated for antiviral effects against norovirus using murine norovirus (MNV) as a model for norovirus [...] Read more.

Phytochemicals provide environmentally friendly and relatively inexpensive natural products, which could potentially benefit public health by controlling human norovirus (HuNoV) infection. In this study, 18 different phytochemicals were evaluated for antiviral effects against norovirus using murine norovirus (MNV) as a model for norovirus biology. Among these phytochemicals, curcumin (CCM) was the most potent anti-noroviral phytochemical, followed by resveratrol (RVT). In a cell culture infection model, exposure to CCM or RVT for 3 days reduced infectivity of norovirus by 91% and 80%, respectively. To confirm the antiviral capability of CCM, we further evaluated its antiviral efficacy at various doses (0.25, 0.5, 0.75, 1, and 2 mg/mL) and durations (short-term: 10, 30, 60, and 120 min; long-term: 1, 3, 7, and 14 days). The anti-noroviral effect of CCM was verified to occur in a dose-dependent manner. Additionally, we evaluated the inhibitory effect of each phytochemical on the replication of HuNoV using a HuNoV replicon-bearing cell line (HG23). Neither CCM nor RVT had a strong inhibitory effect on HuNoV replication, which suggests that their antiviral mechanism may involve viral entry or other life cycle stages rather than the replication of viral RNA. Our results demonstrated that CCM may be a promising candidate for development as an anti-noroviral agent to prevent outbreaks of foodborne illness. Full article

(This article belongs to the Section Natural Products Chemistry)

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48 pages, 10946 KiB

Open AccessArticle

Naturally Occurring Cinnamic Acid Sugar Ester Derivatives

by Yuxin Tian^1,†, Weirui Liu^1,†, Yi Lu², Yan Wang¹, Xiaoyi Chen¹, Shaojuan Bai¹, Yicheng Zhao¹, Ting He¹, Fengxue Lao³, Yinghui Shang³, Yu Guo³ and Gaimei She^1,*

¹ School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing 100102, China

² School of Basic Medicine, Beijing University of Chinese Medicine, Beijing 100102, China

³ Beijing Key Laboratory of Bioactive Substances and Functional Foods, Beijing Union University, Beijing 100191, China

^† These authors contributed equally to this work.

Molecules 2016, 21(10), 1402; https://doi.org/10.3390/molecules21101402 - 24 Oct 2016

Cited by 25 | Viewed by 8996

Abstract

Cinnamic acid sugar ester derivatives (CASEDs) are a class of natural product with one or several phenylacrylic moieties linked with the non-anomeric carbon of a glycosyl skeleton part through ester bonds. Their notable anti-depressant and brains protective activities have made them a topic [...] Read more.

Cinnamic acid sugar ester derivatives (CASEDs) are a class of natural product with one or several phenylacrylic moieties linked with the non-anomeric carbon of a glycosyl skeleton part through ester bonds. Their notable anti-depressant and brains protective activities have made them a topic of great interest over the past several decades. In particular the compound 3′,6-disinapoylsucrose, the index component of Yuanzhi (a well-known Traditional Chinese Medicine or TCM), presents antidepressant effects at a molecular level, and has become a hotspot of research on new lead drug compounds. Several other similar cinnamic acid sugar ester derivatives are reported in traditional medicine as compounds to calm the nerves and display anti-depression and neuroprotective activity. Interestingly, more than one third of CASEDs are distributed in the family Polygalaceae. This overview discusses the isolation of cinnamic acid sugar ester derivatives from plants, together with a systematic discussion of their distribution, chemical structures and properties and pharmacological activities, with the hope of providing references for natural product researchers and draw attention to these interesting compounds. Full article

(This article belongs to the Section Medicinal Chemistry)

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13 pages, 2811 KiB

Open AccessArticle

Seasonal Dynamics of Metabolites in Needles of Taxus wallichiana var. mairei

by Li Yang^1,2, Zan-Sheng Zheng³, Fang Cheng¹, Xiao Ruan¹, De-An Jiang², Cun-De Pan⁴ and Qiang Wang^1,*

¹ Ningbo Institute of Technology, Zhejiang University, Ningbo 315100, China

² College of Life Sciences, Zhejiang University, Hangzhou 310058, China

³ Ningbo Chemgoo Pharmaceutical Technology Innovation Limited, Ningbo 315112, China

⁴ College of Forestry and Horticulture, Xinjiang Agricultural University, Urumqi 830052, China

Molecules 2016, 21(10), 1403; https://doi.org/10.3390/molecules21101403 - 20 Oct 2016

Cited by 42 | Viewed by 6558

Abstract

Seasonal variations of the phytochemicals contents in needles of T. wallichiana var. mairei due to the effects of growth meteorological parameters were investigated in this study. The needles of T. wallichiana var. mairei were collected from different months and the contents of taxoids [...] Read more.

Seasonal variations of the phytochemicals contents in needles of T. wallichiana var. mairei due to the effects of growth meteorological parameters were investigated in this study. The needles of T. wallichiana var. mairei were collected from different months and the contents of taxoids (paclitaxel, 10-deacetylbaccatin III (10-DAB), baccatin III, cephalomannine, 10-deacetyltaxol (10-DAT)), flavones (ginkgetin, amentoflavone, quercetin) and polysaccharides were quantified by ultra performance liquid chromatography (UPLC) and the resonance light scattering (RIL) method. The content of taxoids gave the highest level of 1.77 ± 0.38 mg·g⁻¹ in January, and the lowest value of 0.61 ± 0.08 mg·g⁻¹ in September. Unlike taxoids, the content of flavonoids was the highest in August. The content of polysaccharides reached peak value of 28.52 ± 0.57 mg·g⁻¹ in September, which was two times higher than the lowest content of 9.39 ± 0.17 mg·g⁻¹ in January. The contents of paclitaxel, 10-DAB, 10-DAT and polysaccharides significantly depended on meteorological parameters. The mean of minimum temperature (R = −0.61) and length of daylight (R = −0.60) were significantly correlated to 10-DAB content, while 10-DAT level showed significant correlation with length of daylight (R = −0.70) and relative humidity (R = 0.70). In addition, temperature had significantly negative effect on the content of paclitaxel and a significantly positive effect on that of polysaccharides. This study enriched the knowledge on the accumulation pattern of metabolites and could help us to determine the collecting time of T. wallichiana var. mairei for medicinal use. Full article

(This article belongs to the Section Molecular Diversity)

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20 pages, 2258 KiB

Open AccessReview

Effects of Saponins on Lipid Metabolism: A Review of Potential Health Benefits in the Treatment of Obesity

by Mariangela Marrelli^1,*, Filomena Conforti¹, Fabrizio Araniti²

and Giancarlo A. Statti¹

¹ Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, Rende (CS) I-87036, Italy

² Department of AGRARIA, University “Mediterranea” of Reggio Calabria, Reggio Calabria (RC) I-89124, Italy

Molecules 2016, 21(10), 1404; https://doi.org/10.3390/molecules21101404 - 20 Oct 2016

Cited by 215 | Viewed by 20560

Abstract

Obesity is one of the greatest public health problems. This complex condition has reached epidemic proportions in many parts of the world, and it constitutes a risk factor for several chronic disorders, such as hypertension, cardiovascular diseases and type 2 diabetes. In the [...] Read more.

Obesity is one of the greatest public health problems. This complex condition has reached epidemic proportions in many parts of the world, and it constitutes a risk factor for several chronic disorders, such as hypertension, cardiovascular diseases and type 2 diabetes. In the last few decades, several studies dealt with the potential effects of natural products as new safe and effective tools for body weight control. Saponins are naturally-occurring surface-active glycosides, mainly produced by plants, whose structure consists of a sugar moiety linked to a hydrophobic aglycone (a steroid or a triterpene). Many pharmacological properties have been reported for these compounds, such as anti-inflammatory, immunostimulant, hypocholesterolemic, hypoglycemic, antifungal and cytotoxic activities. The aim of this review is to provide an overview of recent studies about the anti-obesity therapeutic potential of saponins isolated from medicinal plants. Results on the in vitro and in vivo activity of this class of phytochemicals are here presented and discussed. The most interesting findings about their possible mechanism of action and their potential health benefits in the treatment of obesity are reported, as well. Full article

(This article belongs to the Special Issue Natural Products in Anti-Obesity Therapy)

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18 pages, 7033 KiB

Open AccessArticle

Identification of Novel Human Breast Carcinoma (MDA-MB-231) Cell Growth Modulators from a Carbohydrate-Based Diversity Oriented Synthesis Library

by Elena Lenci¹, Riccardo Innocenti¹, Alessio Biagioni²

, Gloria Menchi¹, Francesca Bianchini^2,*

and Andrea Trabocchi^1,*

¹ Department of Chemistry “Ugo Schiff”, University of Florence, Via della Lastruccia 13, 50019 Sesto Fiorentino, Florence, Italy

² Department of Clinical and Experimental Biomedical Science “Mario Serio”, University of Florence, Viale Morgagni 50, 50134 Florence, Italy

Molecules 2016, 21(10), 1405; https://doi.org/10.3390/molecules21101405 - 20 Oct 2016

Cited by 2 | Viewed by 5518

Abstract

The application of a cell-based growth inhibition on a library of skeletally different glycomimetics allowed for the selection of a hexahydro-2H-furo[3,2-b][1,4]oxazine compound as candidate inhibitors of MDA-MB-231 cell growth. Subsequent synthesis of analogue compounds and preliminary biological studies validated [...] Read more.

The application of a cell-based growth inhibition on a library of skeletally different glycomimetics allowed for the selection of a hexahydro-2H-furo[3,2-b][1,4]oxazine compound as candidate inhibitors of MDA-MB-231 cell growth. Subsequent synthesis of analogue compounds and preliminary biological studies validated the selection of a valuable hit compound with a novel polyhydroxylated structure for the modulation of the breast carcinoma cell cycle mechanism. Full article

(This article belongs to the Special Issue Diversity Oriented Synthesis 2016)

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15 pages, 7255 KiB

Open AccessArticle

Capsaicin Suppresses Cell Proliferation, Induces Cell Cycle Arrest and ROS Production in Bladder Cancer Cells through FOXO3a-Mediated Pathways

by Kaiyu Qian^1,2,†, Gang Wang^1,†, Rui Cao¹, Tao Liu^1,3, Guofeng Qian⁴, Xinyuan Guan⁵, Zhongqiang Guo¹, Yu Xiao^1,6,* and Xinghuan Wang^1,*

¹ Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan 430071, China

² Department of Urology, The Fifth Hospital of Wuhan, Wuhan 430050, China

³ Department of Urology, Jingzhou Central Hospital, Jingzhou 434020, China

⁴ Department of Endocrinology, The First Affiliated Hospital of Zhejiang University, Hangzhou 310003, China

⁵ Department of Clinical Oncology, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong, China

⁶ Center for Medical Science Research, Zhongnan Hospital of Wuhan University, Wuhan 430071, China

^† These authors contributed equally to this work.

Molecules 2016, 21(10), 1406; https://doi.org/10.3390/molecules21101406 - 21 Oct 2016

Cited by 52 | Viewed by 9007 | Correction

Abstract

Capsaicin (CAP), a highly selective agonist for transient receptor potential vanilloid type 1 (TRPV1), has been widely reported to exhibit anti-oxidant, anti-inflammation and anticancer activities. Currently, several therapeutic approaches for bladder cancer (BCa) are available, but accompanied by unfavorable outcomes. Previous studies reported [...] Read more.

Capsaicin (CAP), a highly selective agonist for transient receptor potential vanilloid type 1 (TRPV1), has been widely reported to exhibit anti-oxidant, anti-inflammation and anticancer activities. Currently, several therapeutic approaches for bladder cancer (BCa) are available, but accompanied by unfavorable outcomes. Previous studies reported a potential clinical effect of CAP to prevent BCa tumorigenesis. However, its underlying molecular mechanism still remains unknown. Our transcriptome analysis suggested a close link among calcium signaling pathway, cell cycle regulation, ROS metabolism and FOXO signaling pathway in BCa. In this study, several experiments were performed to investigate the effects of CAP on BCa cells (5637 and T24) and NOD/SCID mice. Our results showed that CAP could suppress BCa tumorigenesis by inhibiting its proliferation both in vitro and in vivo. Moreover, CAP induced cell cycle arrest at G0/G1 phase and ROS production. Importantly, our studies revealed a strong increase of FOXO3a after treatment with CAP. Furthermore, we observed no significant alteration of apoptosis by CAP, whereas Catalase and SOD2 were considerably upregulated, which could clear ROS and protect against cell death. Thus, our results suggested that CAP could inhibit viability and tumorigenesis of BCa possibly via FOXO3a-mediated pathways. Full article

(This article belongs to the Special Issue Capsaicin)

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13 pages, 3971 KiB

Open AccessArticle

Design, Synthesis and Biological Evaluation of 6-(2,6-Dichloro-3,5-dimethoxyphenyl)-4-substituted-1H-indazoles as Potent Fibroblast Growth Factor Receptor Inhibitors

by Zhen Zhang^1,2, Dongmei Zhao^1,*, Yang Dai³, Maosheng Cheng¹, Meiyu Geng³, Jingkang Shen², Yuchi Ma^2,*, Jing Ai^3,* and Bing Xiong^2,*

¹ Key Laboratory of Structure-Based Drug Design & Discovery of Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, China

² Department of Medicinal Chemistry, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai 201203, China

³ Division of Anti-Tumor Pharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai 201203, China

Molecules 2016, 21(10), 1407; https://doi.org/10.3390/molecules21101407 - 23 Oct 2016

Cited by 14 | Viewed by 6653

Abstract

Tyrosine kinase fibroblast growth factor receptor (FGFR), which is aberrant in various cancer types, is a promising target for cancer therapy. Here we reported the design, synthesis, and biological evaluation of a new series of 6-(2,6-dichloro-3,5-dimethoxyphenyl)-4-substituted-1H-indazole derivatives as potent FGFR inhibitors. [...] Read more.

Tyrosine kinase fibroblast growth factor receptor (FGFR), which is aberrant in various cancer types, is a promising target for cancer therapy. Here we reported the design, synthesis, and biological evaluation of a new series of 6-(2,6-dichloro-3,5-dimethoxyphenyl)-4-substituted-1H-indazole derivatives as potent FGFR inhibitors. The compound 6-(2,6-dichloro-3,5-dimethoxyphenyl)-N-phenyl-1H-indazole-4-carboxamide (10a) was identified as a potent FGFR1 inhibitor, with good enzymatic inhibition. Further structure-based optimization revealed that 6-(2,6-dichloro-3,5-dimethoxyphenyl)-N-(3-(4-methylpiperazin-1-yl)phenyl)-1H-indazole-4-carboxamide (13a) is the most potent FGFR1 inhibitor in this series, with an enzyme inhibitory activity IC₅₀ value of about 30.2 nM. Full article

(This article belongs to the Special Issue Kinase Inhibitor Chemistry)

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11 pages, 1026 KiB

Open AccessCommunication

Original Synthesis of Fluorenyl Alcohol Derivatives by Reductive Dehalogenation Initiated by TDAE

by Alain Gamal Giuglio-Tonolo, Thierry Terme and Patrice Vanelle^*

Aix-Marseille Université, CNRS, Institut de Chimie Radicalaire ICR, UMR 7273, Laboratoire de Pharmaco-Chimie Radicalaire, Marseille 13385, France

Molecules 2016, 21(10), 1408; https://doi.org/10.3390/molecules21101408 - 24 Oct 2016

Cited by 4 | Viewed by 6645

Abstract

We report here a novel and easy-to-handle reductive dehalogenation of 9-bromofluorene in the presence of arylaldehydes and dicarbonyl derivatives to give the corresponding fluorenyl alcohol derivatives and Darzens epoxides as by-products in tetrakis(dimethylamino)ethylene (TDAE) reaction conditions. The reaction is believed to proceed via [...] Read more.

We report here a novel and easy-to-handle reductive dehalogenation of 9-bromofluorene in the presence of arylaldehydes and dicarbonyl derivatives to give the corresponding fluorenyl alcohol derivatives and Darzens epoxides as by-products in tetrakis(dimethylamino)ethylene (TDAE) reaction conditions. The reaction is believed to proceed via two successive single electron transfers to generate the fluorenyl anion which was able to react with different electrophiles. A mechanistic study was conducted to understand the formation of the epoxide derivatives. Full article

(This article belongs to the Section Organic Chemistry)

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13 pages, 2288 KiB

Open AccessArticle

A Fast and Robust UHPLC-MRM-MS Method to Characterize and Quantify Grape Skin Tannins after Chemical Depolymerization

by Lucie Pinasseau¹, Arnaud Verbaere¹, Maryline Roques^1,2,3, Emmanuelle Meudec¹, Anna Vallverdú-Queralt¹

, Nancy Terrier², Jean-Claude Boulet¹, Véronique Cheynier¹ and Nicolas Sommerer^1,*

¹ Plate-Forme D’analyse des Polyphénols, UMR1083 Sciences Pour l’Œnologie, Institut National de la Recherche Agronomique, Montpellier 34060, France

² Equipe Biosynthèse et Composition en Polyphénols et Polysaccharides, UMR1083 Sciences Pour l’Œnologie, Institut National de la Recherche Agronomique, Montpellier 34060, France

³ Institut Français de la Vigne et du Vin, Pôle National Matériel Végétal, UMT Génovigne, Montpellier 34060, France

Molecules 2016, 21(10), 1409; https://doi.org/10.3390/molecules21101409 - 21 Oct 2016

Cited by 27 | Viewed by 8136

Abstract

A rapid, sensitive, and selective analysis method using ultra high performance liquid chromatography coupled with triple-quadrupole mass spectrometry (UHPLC-QqQ-MS) has been developed for the characterization and quantification of grape skin flavan-3-ols after acid-catalysed depolymerization in the presence of phloroglucinol (phloroglucinolysis). The compound detection [...] Read more.

A rapid, sensitive, and selective analysis method using ultra high performance liquid chromatography coupled with triple-quadrupole mass spectrometry (UHPLC-QqQ-MS) has been developed for the characterization and quantification of grape skin flavan-3-ols after acid-catalysed depolymerization in the presence of phloroglucinol (phloroglucinolysis). The compound detection being based on specific MS transitions in Multiple Reaction Monitoring (MRM) mode, this fast gradient robust method allows analysis of constitutive units of grape skin proanthocyanidins, including some present in trace amounts, in a single injection, with a throughput of 6 samples per hour. This method was applied to a set of 214 grape skin samples from 107 different red and white grape cultivars grown under two conditions in the vineyard, irrigated or non-irrigated. The results of triplicate analyses confirmed the robustness of the method, which was thus proven to be suitable for high-throughput and large-scale metabolomics studies. Moreover, these preliminary results suggest that analysis of tannin composition is relevant to investigate the genetic bases of grape response to drought. Full article

(This article belongs to the Special Issue Flavonoids: From Structure to Health Issues)

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16 pages, 1519 KiB

Open AccessArticle

Potential Anticancer Effects of Polyphenols from Chestnut Shell Extracts: Modulation of Cell Growth, and Cytokinomic and Metabolomic Profiles

by Angela Sorice^1,†, Francesco Siano^2,†

, Francesca Capone¹, Eliana Guerriero¹, Gianluca Picariello², Alfredo Budillon¹, Gennaro Ciliberto³, Marina Paolucci⁴

, Susan Costantini^1,* and Maria Grazia Volpe^2,*

¹ CROM, Istituto Nazionale Tumori “Fondazione G. Pascale”—IRCCS, Napoli 80131, Italy

² Consiglio Nazionale delle Ricerche, Istituto di Scienze dell’Alimentazione, Via Roma 64, Avellino 83100, Italy

³ Direttore Scientifico, IRCCS Istituto Nazionale Tumori “Fondazione G. Pascale”, Napoli 80131, Italy

⁴ Dipartimento di Scienze e Tecnologie, Università degli Studi del Sannio, Via Port’Arsa 11, Benevento 82100, Italy

^† These authors contributed equally to this work.

Molecules 2016, 21(10), 1411; https://doi.org/10.3390/molecules21101411 - 21 Oct 2016

Cited by 64 | Viewed by 7385

Abstract

In this study, a hydroalcoholic chestnut shell extract was characterized and tested on six different human cell lines. Gallic, ellagic, and syringic acids were the most abundant non-condensed compounds in the chestnut extract, as determined by high performance liquid chromatography (HPLC). Tannins were [...] Read more.

In this study, a hydroalcoholic chestnut shell extract was characterized and tested on six different human cell lines. Gallic, ellagic, and syringic acids were the most abundant non-condensed compounds in the chestnut extract, as determined by high performance liquid chromatography (HPLC). Tannins were mainly represented by condensed monomeric units of epigallocatechin and catechin/epicatechin. After 48 h of treatment, only the human hepatoblastoma HepG2 cells reached an inhibition corresponding to IC₅₀ with an increase of apoptosis and mitochondrial depolarization. The cytokinome evaluation before and after treatment revealed that the vascular endothelial growth factor (VEGF) and the tumor necrosis factor (TNF)-α decreased after the treatment, suggesting a potential anti-angiogenic and anti-inflammatory effect of this extract. Moreover, the metabolome evaluation by ¹H-NMR evidenced that the polyphenols extracted from chestnut shell (PECS) treatment affected the levels of some amino acids and other metabolites. Overall, these data highlight the effects of biomolecules on cell proliferation, apoptosis, cell cycle and mitochondrial depolarization, and on cytokinomics and metabolomics profiles. Full article

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2 pages, 563 KiB

Open AccessCorrection

Correction: Chae, H.S.; et al. Atractylodin Inhibits Interleukin-6 by Blocking NPM-ALK Activation and MAPKs in HMC-1. Molecules 2016, 21, 1169

by Hee-Sung Chae, Young-Mi Kim and Young-Won Chin^*

College of Pharmacy, Dongguk University-Seoul, 32 Dongguk-lo, Ilsandong-gu, Goyang-si, Gyeonggi-do 410-820, Korea

Molecules 2016, 21(10), 1412; https://doi.org/10.3390/molecules21101412 - 25 Oct 2016

Cited by 2 | Viewed by 3475

Abstract

The authors wish to make the following correction to their paper [1].[...] Full article

(This article belongs to the Section Natural Products Chemistry)

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2 pages, 729 KiB

Open AccessCorrection

Correction: Chae, H.S., et al. Anti-Inflammatory Effects of 6,8-Diprenyl-7,4′-dihydroxyflavanone from Sophora tonkinensis on Lipopolysaccharide-Stimulated RAW 264.7 Cells. Molecules. 2016, 21, 1049.

by Hee-Sung Chae¹, Hunseung Yoo², Young-Mi Kim¹, Young Hee Choi¹

, Chang Hoon Lee¹ and Young-Won Chin^1,*

¹ College of Pharmacy, Dongguk University-Seoul, 32 Dongguk-lo, Ilsandong-gu, Goyang-si, Gyeonggi-do 410-820, Korea

² New Drug Preclinical & Analytical Team, Life Science R & D Center, SK Chemicals, 310 Pangyo-ro 463-400, Korea

Molecules 2016, 21(10), 1413; https://doi.org/10.3390/molecules21101413 - 24 Oct 2016

Cited by 3 | Viewed by 3810

Abstract

n/a Full article

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20 pages, 703 KiB

Open AccessArticle

Laurus nobilis, Zingiber officinale and Anethum graveolens Essential Oils: Composition, Antioxidant and Antibacterial Activities against Bacteria Isolated from Fish and Shellfish

by Mejdi Snuossi¹

, Najla Trabelsi², Sabrine Ben Taleb¹, Ameni Dehmeni¹, Guido Flamini³

and Vincenzo De Feo^4,*

¹ Laboratoire de Traitement et Valorisation des Rejets Hydriques (LR 15 CERTEO5), Technopole de Borj-Cédria, BP 273, Soliman 8020, Tunisie

² Laboratoire de Biotechnologie de l’Olivier, Centre de Technologie de Borj-Cédria, BP 901, Hammam Lif 2050, Tunisie

³ Department of Pharmacy, University of Pisa, Via Bonanno 33, Pisa 56126, Italy

⁴ Department of Pharmacy, University of Salerno, Via Giovanni Paolo II 132, Fisciano 84084, Salerno, Italy

Molecules 2016, 21(10), 1414; https://doi.org/10.3390/molecules21101414 - 22 Oct 2016

Cited by 61 | Viewed by 11140

Abstract

Several bacterial strains were isolated from wild and reared fish and shellfish. The identification of these strains showed the dominance of the Aeromonas hydrophila species in all seafood samples, followed by Staphylococcus spp., Vibrio alginolyticus, Enterobacter cloacae, Klebsiella ornithinolytica, Klebsiella [...] Read more.

Several bacterial strains were isolated from wild and reared fish and shellfish. The identification of these strains showed the dominance of the Aeromonas hydrophila species in all seafood samples, followed by Staphylococcus spp., Vibrio alginolyticus, Enterobacter cloacae, Klebsiella ornithinolytica, Klebsiella oxytoca and Serratia odorifera. The isolates were studied for their ability to produce exoenzymes and biofilms. The chemical composition of the essential oils from Laurus nobilis leaves, Zingiber officinale rhizomes and Anethum graveolens aerial parts was studied by GC and GC/MS. The essential oils’ antioxidant and antibacterial activities against the isolated microorganisms were studied. Low concentrations of the three essential oils were needed to inhibit the growth of the selected bacteria and the lowest MBCs values were obtained for the laurel essential oil. The selected essential oils can be used as a good natural preservative in fish food due to their antioxidant and antibacterial activities. Full article

(This article belongs to the Collection Recent Advances in Flavors and Fragrances)

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9 pages, 628 KiB

Open AccessArticle

Isobutylhydroxyamides from Zanthoxylum bungeanum and Their Suppression of NO Production

by Yuan Wang^1,2, Chun-Huan Li¹, Bo Luo¹, Ya Nan Sun³, Young Ho Kim³, An-Zhi Wei^2,* and Jin-Ming Gao^1,*

¹ Shaanxi Key Laboratory of Natural Products & Chemical Biology, College of Science, Northwest A&F University, Yangling 712100, Shaanxi, China

² College of Forestry, Northwest A&F University, Yangling 712100, Shaanxi, China

³ College of Pharmacy, Chungnam National University, Daejeon 305-764, Korea

Molecules 2016, 21(10), 1416; https://doi.org/10.3390/molecules21101416 - 23 Oct 2016

Cited by 42 | Viewed by 6980

Abstract

Four new unsaturated aliphatic acid amides, named zanthoamides A–D (1–4), and eight known ones—tetrahydrobungeanool (5), ZP-amide A (6), ZP-amide B (7), ZP-amide C (8), ZP-amide D (9), ZP-amide E [...] Read more.

Four new unsaturated aliphatic acid amides, named zanthoamides A–D (1–4), and eight known ones—tetrahydrobungeanool (5), ZP-amide A (6), ZP-amide B (7), ZP-amide C (8), ZP-amide D (9), ZP-amide E (10), bugeanumamide A (11), and (2E,7E,9E)-N-(2-hydroxy-2-methylpropyl)-6,11-dioxo-2,7,9-dodecatrienamide (12)—were isolated from the pericarps of Zanthoxylum bungeanum. The structures of these compounds were elucidated by extensive use of spectroscopic methods, including HRESIMS, 1D and 2D NMR analyses and comparison with previously reported data. Compound 4 contained a rare C₆ fatty acid unit with an acetal group. Results revealed that compounds 1, 5, 6, and 12 showed inhibitory effects on nitric oxide (NO) production in LPS-stimulated RAW 264.7 macrophages, with IC₅₀values of 48.7 ± 0.32, 27.1 ± 1.15, 49.8 ± 0.38, and 39.4 ± 0.63 µM, respectively, while the other compounds were inactive (IC₅₀ > 60 μM). They could contribute to the anti-inflammatory effects of Z. bungeanum by suppression of NO production. Full article

(This article belongs to the Collection Bioactive Compounds)

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22 pages, 2653 KiB

Open AccessArticle

Exogenous Methyl Jasmonate and Salicylic Acid Induce Subspecies-Specific Patterns of Glucosinolate Accumulation and Gene Expression in Brassica oleracea L.

by Go-Eun Yi^1,†, Arif Hasan Khan Robin^1,†

, Kiwoung Yang^1,†, Jong-In Park¹, Byung Ho Hwang² and Ill-Sup Nou^1,*

¹ Department of Horticulture, Sunchon National University, Suncheon-si 540-950, Korea

² R & D Center for Crop Breeding, Asia Seed Ltd., Icheon-si, Gyeonggi-do 467-906, Korea

^† These authors contributed equally to this work.

Molecules 2016, 21(10), 1417; https://doi.org/10.3390/molecules21101417 - 24 Oct 2016

Cited by 63 | Viewed by 8403

Abstract

Glucosinolates have anti-carcinogenic properties. In the recent decades, the genetics of glucosinolate biosynthesis has been widely studied, however, the expression of specific genes involved in glucosinolate biosynthesis under exogenous phytohormone treatment has not been explored at the subspecies level in Brassica oleracea. [...] Read more.

Glucosinolates have anti-carcinogenic properties. In the recent decades, the genetics of glucosinolate biosynthesis has been widely studied, however, the expression of specific genes involved in glucosinolate biosynthesis under exogenous phytohormone treatment has not been explored at the subspecies level in Brassica oleracea. Such data are vital for strategies aimed at selective exploitation of glucosinolate profiles. This study quantified the expression of 38 glucosinolate biosynthesis-related genes in three B. oleracea subspecies, namely cabbage, broccoli and kale, and catalogued associations between gene expression and increased contents of individual glucosinolates under methyl jasmonate (MeJA) and salicylic acid (SA) treatments. Glucosinolate accumulation and gene expression in response to phytohormone elicitation was subspecies specific. For instance, cabbage leaves showed enhanced accumulation of the aliphatic glucoiberin, progoitrin, sinigrin and indolic neoglucobrassicin under both MeJA and SA treatment. MeJA treatment induced strikingly higher accumulation of glucobrassicin (GBS) in cabbage and kale and of neoglucobrassicin (NGBS) in broccoli compared to controls. Notably higher expression of ST5a (Bol026200), CYP81F1 (Bol028913, Bol028914) and CYP81F4 genes was associated with significantly higher GBS accumulation under MeJA treatment compared to controls in all three subspecies. CYP81F4 genes, trans-activated by MYB34 genes, were expressed at remarkably high levels in all three subspecies under MeJA treatment, which also induced in higher indolic NGBS accumulation in all three subspecies. Remarkably higher expression of MYB28 (Bol036286), ST5b, ST5c, AOP2, FMOGS-OX5 (Bol031350) and GSL-OH (Bol033373) was associated with much higher contents of aliphatic glucosinolates in kale leaves compared to the other two subspecies. The genes expressed highly could be utilized in strategies to selectively increase glucosinolate compounds in B. oleracea subspecies. These results promote efforts to develop genotypes of B. oleracea and other species with enhanced levels of desired glucosinolates. Full article

(This article belongs to the Section Molecular Diversity)

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Molecules, Volume 21, Issue 10 (October 2016) – 153 articles

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